Aryl carbonyl derivatives as therapeutic agents

ABSTRACT

This invention relates to aryl carbonyl derivatives which are activators of glucokinase which may be useful for the management, treatment, control, or adjunct treatment of diseases, where increasing glucokinase activity is beneficial.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.10/679,887, filed Oct. 6, 2003, which was a continuation of theInternational Application No. PCT/DK03/00449, filed Jun. 27, 2003, whichclaimed priority under 35 U.S.C. 119 of Danish Application No. PA 200200999 filed Jun. 27, 2002, and Danish Application No. PA 2003 00286,filed Feb. 25, 2003, and U.S. Application No. 60/394,144, filed Jul. 3,2002, and U.S. Application No. 60/452,228, filed Mar. 5, 2003, thecontents of each of which are fully incorporated herein by reference.

FIELD OF THE INVENTION

This invention relates to compounds which are activators of glucokinase(GK), which may be useful for the management, treatment, control, oradjunct treatment of diseases, where increasing glucokinase activity isbeneficial.

BACKGROUND OF THE INVENTION

Diabetes is characterised by an impaired glucose metabolism manifestingitself among other things by an elevated blood glucose level in thediabetic patients. Underlying defects lead to a classification ofdiabetes into two major groups: Type 1 diabetes, or insulin demandingdiabetes mellitus (IDDM), which arises when patients lack β-cellsproducing insulin in their pancreatic glands, and type 2 diabetes, ornon-insulin dependent diabetes mellitus (NIDDM), which occurs inpatients with an impaired β-cell function besides a range of otherabnormalities.

Type 1 diabetic patients are currently treated with insulin, while themajority of type 2 diabetic patients are treated either withsulphonylureas that stimulate β-cell function or with agents thatenhance the tissue sensitivity of the patients towards insulin or withinsulin. Among the agents applied to enhance tissue sensitivity towardsinsulin metformin is a representative example.

Even though sulphonylureas are widely used in the treatment of NIDDMthis therapy is, in most instances, not satisfactory: In a large numberof NIDDM patients sulphonylureas do not suffice to normalise blood sugarlevels and the patients are, therefore, at high risk for acquiringdiabetic complications. Also, many patients gradually lose the abilityto respond to treatment with sulphonylureas and are thus graduallyforced into insulin treatment. This shift of patients from oralhypoglycaemic agents to insulin therapy is usually ascribed toexhaustion of the β-cells in NIDDM patients.

In normal subjects as well as in diabetic subjects, the liver producesglucose in order to avoid hypoglycaemia. This glucose production isderived either from the release of glucose from glycogen stores or fromgluconeogenesis, which is a de novo intracellular synthesis of glucose.In type 2 diabetes, however, the regulation of hepatic glucose output ispoorly controlled and is increased, and may be doubled after anovernight fast. Moreover, in these patients there exists a strongcorrelation between the increased fasting plasma glucose levels and therate of hepatic glucose production. Similarly, hepatic glucoseproduction will be increased in type 1 diabetes, if the disease is notproperly controlled by insulin treatment.

Since existing forms of therapy of diabetes does not lead to sufficientglycaemic control and therefore are unsatisfactory, there is a greatdemand for novel therapeutic approaches.

Atherosclerosis, a disease of the arteries, is recognized to be theleading cause of death in the United States and Western Europe. Thepathological sequence leading to atherosclerosis and occlusive heartdisease is well known. The earliest stage in this sequence is theformation of “fatty streaks” in the carotid, coronary and cerebralarteries and in the aorta. These lesions are yellow in colour due to thepresence of lipid deposits found principally within smooth-muscle cellsand in macrophages of the intima layer of the arteries and aorta.Further, it is postulated that most of the cholesterol found within thefatty streaks, in turn, give rise to development of the “fibrousplaque”, which consists of accumulated intimal smooth muscle cells ladenwith lipid and surrounded by extra-cellular lipid, collagen, elastin andproteoglycans. The cells plus matrix form a fibrous cap that covers adeeper deposit of cell debris and more extracellular lipid. The lipid isprimarily free and esterified cholesterol. The fibrous plaque formsslowly, and is likely in time to become calcified and necrotic,advancing to the “complicated lesion” which accounts for the arterialocclusion and tendency toward mural thrombosis and arterial muscle spasmthat characterize advanced atherosclerosis.

Epidemiological evidence has firmly established hyperlipidemia as aprimary risk factor in causing cardiovascular disease (CVD) due toatherosclerosis. In recent years, leaders of the medical profession haveplaced renewed emphasis on lowering plasma cholesterol levels, and lowdensity lipoprotein cholesterol in particular, as an essential step inprevention of CVD. The upper limits of “normal” are now known to besignificantly lower than heretofore appreciated. As a result, largesegments of Western populations are now realized to be at particularhigh risk. Independent risk factors include glucose intolerance, leftventricular hypertrophy, hypertension, and being of the male sex.Cardiovascular disease is especially prevalent among diabetic subjects,at least in part because of the existence of multiple independent riskfactors in this population. Successful treatment of hyperlipidemia inthe general population, and in diabetic subjects in particular, istherefore of exceptional medical importance.

Hypertension (or high blood pressure) is a condition, which occurs inthe human population as a secondary symptom to various other disorderssuch as renal artery stenosis, pheochromocytoma, or endocrine disorders.However, hypertension is also evidenced in many patients in whom thecausative agent or disorder is unknown. While such “essential”hypertension is often associated with disorders such as obesity,diabetes, and hypertriglyceridemia, the relationship between thesedisorders has not been elucidated. Additionally, many patients displaythe symptoms of high blood pressure in the complete absence of any othersigns of disease or disorder.

It is known that hypertension can directly lead to heart failure, renalfailure, and stroke (brain haemorrhaging). These conditions are capableof causing short-term death in a patient. Hypertension can alsocontribute to the development of atherosclerosis and coronary disease.These conditions gradually weaken a patient and can lead to long-termdeath.

The exact cause of essential hypertension is unknown, though a number offactors are believed to contribute to the onset of the disease. Amongsuch factors are stress, uncontrolled emotions, unregulated hormonerelease (the renin, angiotensin aldosterone system), excessive salt andwater due to kidney malfunction, wall thickening and hypertrophy of thevasculature resulting in constricted blood vessels and genetic factors.

The treatment of essential hypertension has been undertaken bearing theforegoing factors in mind. Thus a broad range of beta-blockers,vasoconstrictors, angiotensin converting enzyme inhibitors and the likehave been developed and marketed as antihypertensives. The treatment ofhypertension utilizing these compounds has proven beneficial in theprevention of short-interval deaths such as heart failure, renalfailure, and brain haemorrhaging. However, the development ofatherosclerosis or heart disease due to hypertension over a long periodof time remains a problem. This implies that although high bloodpressure is being reduced, the underlying cause of essentialhypertension is not responding to this treatment.

Hypertension has been associated with elevated blood insulin levels, acondition known as hyperinsulinemia. Insulin, a peptide hormone whoseprimary actions are to promote glucose utilization, protein synthesisand the formation and storage of neutral lipids, also acts to promotevascular cell growth and increase renal sodium retention, among otherthings. These latter functions can be accomplished without affectingglucose levels and are known causes of hypertension. Peripheralvasculature growth, for example, can cause constriction of peripheralcapillaries, while sodium retention increases blood volume. Thus, thelowering of insulin levels in hyperinsulinemics can prevent abnormalvascular growth and renal sodium retention caused by high insulin levelsand thereby alleviates hypertension.

Cardiac hypertrophy is a significant risk factor in the development ofsudden death, myocardial infarction, and congestive heart failure.Theses cardiac events are due, at least in part, to increasedsusceptibility to myocardial injury after ischemia and reperfusion,which can occur in out-patient as well as perioperative settings. Thereis an unmet medical need to prevent or minimize adverse myocardialperioperative outcomes, particularly perioperative myocardialinfarction. Both non-cardiac and cardiac surgery are associated withsubstantial risks for myocardial infarction or death. Some 7 millionpatients undergoing non-cardiac surgery are considered to be at risk,with incidences of perioperative death and serious cardiac complicationsas high as 20-25% in some series. In addition, of the 400,000 patientsundergoing coronary by-pass surgery annually, perioperative myocardialinfarction is estimated to occur in 5% and death in 1-2%. There iscurrently no drug therapy in this area, which reduces damage to cardiactissue from perioperative myocardial ischemia or enhances cardiacresistance to ischemic episodes. Such a therapy is anticipated to belife-saving and reduce hospitalizations, enhance quality of life andreduce overall health care costs of high risk patients.

Obesity is a well-known risk factor for the development of many verycommon diseases such as atherosclerosis, hypertension, and diabetes. Theincidence of obese people and thereby also these diseases is increasingthroughout the entire industrialised world. Except for exercise, dietand food restriction no convincing pharmacological treatment forreducing body weight effectively and acceptably currently exist.However, due to its indirect but important effect as a risk factor inmortal and common diseases it will be important to find treatment forobesity and/or means of appetite regulation.

The term obesity implies an excess of adipose tissue. In this contextobesity is best viewed as any degree of excess adiposity that imparts ahealth risk. The cut off between normal and obese individuals can onlybe approximated, but the health risk imparted by the obesity is probablya continuum with increasing adiposity. The Framingham study demonstratedthat a 20% excess over desirable weight clearly imparted a health risk(Mann GV N. Engl. J. Med 291:226, 1974). In the United States a NationalInstitutes of Health consensus panel on obesity agreed that a 20%increase in relative weight or a body mass index (BMI=body weight inkilograms divided by the square of the height in meters) above the 85thpercentile for young adults constitutes a health risk. By the use ofthese criteria 20 to 30 percent of adult men and 30 to 40 percent ofadult women in the United States are obese. (NIH, Ann Intern Med103:147, 1985).

Even mild obesity increases the risk for premature death, diabetes,hypertension, atherosclerosis, gallbladder disease, and certain types ofcancer. In the industrialised western world the prevalence of obesityhas increased significantly in the past few decades. Because of the highprevalence of obesity and its health consequences, its prevention andtreatment should be a high public health priority.

When energy intake exceeds expenditure, the excess calories are storedin adipose tissue, and if this net positive balance is prolonged,obesity results, i.e. there are two components to weight balance, and anabnormality on either side (intake or expenditure) can lead to obesity.

The regulation of eating behaviour is incompletely understood. To someextent appetite is controlled by discrete areas in the hypothalamus: afeeding centre in the ventrolateral nucleus of the hypothalamus (VLH)and a satiety centre in the ventromedial hypothalamus (VMH). Thecerebral cortex receives positive signals from the feeding centre thatstimulate eating, and the satiety centre modulates this process bysending inhibitory impulses to the feeding centre. Several regulatoryprocesses may influence these hypothalamic centres. The satiety centremay be activated by the increases in plasma glucose and/or insulin thatfollow a meal. Meal-induced gastric distension is another possibleinhibitory factor. Additionally the hypothalamic centres are sensitiveto catecholamines, and beta-adrenergic stimulation inhibits eatingbehaviour. Ultimately, the cerebral cortex controls eating behaviour,and impulses from the feeding centre to the cerebral cortex are only oneinput. Psychological, social, and genetic factors also influence foodintake.

At present a variety of techniques are available to effect initialweight loss. Unfortunately, initial weight loss is not an optimaltherapeutic goal. Rather, the problem is that most obese patientseventually regain their weight. An effective means to establish and/orsustain weight loss is the major challenge in the treatment of obesitytoday.

WO 00/58293, WO 01/44216, WO/0183465, WO/0183478, WO/0185706, WO01/85707, and WO02/08209, to Hoffman-La Roche, discloses compounds asglucokinase activators.

SUMMARY OF THE INVENTION

This invention provides amide derivatives of the general formula (I), asdescribed below, as activators of glucokinase. The compounds of thepresent invention are useful as activators of glucokinase and thus areuseful for the management, treatment, control and adjunct treatment ofdiseases where increasing the activity of glucokinase is beneficial.Such diseases include type I diabetes and type II diabetes. The presentinvention provides compounds as described below, pharmaceuticalcompositions comprising the compounds, their use for increasing theactivity of glucokinase, their use in preparation of a medicament fortreating said diseases and conditions and the use of compounds orpharmaceutical preparations of the present invention for treating saiddiseases and conditions as well as methods for treating said diseasesand conditions, which methods comprise administering to a subject inneed thereof an effective amount of a compound according to the presentinvention.

The present invention also provides glucokinase activators, for instanceof the general formula (I), which are glucose sensitive glucokinaseactivators, that is, glucokinase activators, the activity of whichdecreases with increasing glucose concentrations.

The present invention also provides glucokinase activators, for instanceof the general formula (I), which are liver specific glucokinaseactivators, that is, glucokinase activators which increase glucoseutilization in the liver (i.e. increase glycogen deposition) withoutinducing any increase in insulin secretion in response to glucose.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for treatment ofmetabolic disorders.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for blood glucoselowering.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for prevention ofhyperglycemia.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for treatment of impairedglucose tolerance IGT.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for treatment of SyndromeX.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for the treatment ofimpaired fasting glucose (IFG).

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for treatment of type 2diabetes.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for treatment of type 1diabetes.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for delaying theprogression of impaired glucose tolerance (IGT) to type 2 diabetes.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for delaying theprogression of non-insulin requiring type 2 diabetes to insulinrequiring type 2 diabetes.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for treatment ofdyslipidemia or hyper-lipidemia.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for treatment ofhypertension.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for the treatment ofobesity.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for lowering of foodintake

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for appetite regulation.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for regulating feedingbehaviour.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for enhancing thesecretion of enteroincretins, such as GLP-1.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for the adjuvanttreatment of type 1 diabetes for preventing the onset of diabeticcomplications.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for increasing the numberand/or the size of beta cells in a mammalian subject.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for treatment of betacell degeneration, in particular apoptosis of beta cells.

The present invention provides the use of a compound or a pharmaceuticalpreparation according to the present invention for treatment offunctional dyspepsia, in particular irritable bowel syndrome.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for treatment ofmetabolic disorders.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for blood glucoselowering.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for the treatmentof hyperglycemia.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for the treatmentof IGT.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for the treatmentof Syndrome X.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for the treatmentof impaired fasting glucose (IFG).

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for the treatmentof type 2 diabetes.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for the treatmentof type 1 diabetes.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for delaying theprogression of impaired glucose tolerance (IGT) to type 2 diabetes.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for delaying theprogression of non-insulin requiring type 2 diabetes to insulinrequiring type 2 diabetes.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for the treatmentof dyslipidemia.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for the treatmentof hyperlipidemia.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for the treatmentof hypertension.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for lowering offood intake.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for appetiteregulation.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for the treatmentof obesity.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for regulatingfeeding behaviour.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for enhancing thesecretion of enteroincretins, such as GLP-1.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for the adjuvanttreatment of type 1 diabetes for preventing the onset of diabeticcomplications.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for increasing thenumber and/or the size of beta cells in a mammalian subject.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for treatment ofbeta cell degeneration, in particular apoptosis of beta cells.

The present invention provides the use of a compound according to thepresent invention for the preparation of a medicament for treatment offunctional dyspepsia, in particular irritable bowel syndrome.

The present invention provides a method of preventing hypoglycaemiacomprising administration of a liver-specific glucokinas activator.

The present invention provides the use of a liver-specific glucokinasactivator for the preparation of a medicament for the prevention ofhypoglycaemia.

Other embodiments and aspects are as defined below and by the appendedclaims.

DEFINITIONS

In the structural formulas given herein and throughout the presentspecification, the following terms have the indicated meaning:

The term “optionally substituted” as used herein means that the group inquestion is either unsubstituted or substituted with one or more of thesubstituents specified. When the group in question are substituted withmore than one substituent the substituent may be the same or different.

The term “adjacent” as used herein regards the relative positions of twoatoms or variables, these two atoms or variables sharing a bond or onevariable preceding or succeeding the other in a variable specification.By way of example, “atom A adjacent to atom B” means that the two atomsA and B share a bond.

The term “halogen” or “halo” means fluorine, chlorine, bromine oriodine.

The term “perhalomethyl” means trifluoromethyl, trichloromethyl,tribromomethyl, or triiodomethyl.

The use of prefixes of this structure: C_(x-y)-alkyl, C_(x-y)-alkenyl,C_(x-y)-alkynyl, C_(x-y)-cycloalkyl orC_(x-y)-cycloalkyl-C_(x-y)-alkenyl- designates radical of the designatedtype having from x to y carbon atoms.

The term “alkyl” as used herein, alone or in combination, refers to astraight or branched chain saturated monovalent hydrocarbon radicalhaving from one to ten carbon atoms, for example C₁₋₈-alkyl orC₁₋₆-alkyl. Typical C₁₋₈-alkyl groups and C₁₋₆-alkyl groups include, butare not limited to e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl,sec-butyl, isobutyl, tert-butyl, n-pentyl, 2-methylbutyl, 3-methylbutyl,4-methylpentyl, neopentyl, n-pentyl, n-hexyl, 1,2-dimethylpropyl,2,2-dimethylpropyl, 1,2,2-trimethylpropyl and the like. The term“C₁₋₈-alkyl” as used herein also includes secondary C₃₋₈-alkyl andtertiary C₄₋₈-alkyl. The term “C₁₋₆-alkyl” as used herein also includessecondary C₃₋₆-alkyl and tertiary C₄₋₆-alkyl.

The term “alkylene” as used herein, alone or in combination, refers to astraight or branched chain saturated divalent hydrocarbon radical havingfrom one to ten carbon atoms, for example C₁₋₈-alkylene orC₁₋₆-alkylene. Examples of “alkylene” as used herein include, but arenot limited to, methylene, ethylene, and the like.

The term “alkenyl” as used herein, alone or in combination, refers to astraight or branched chain monovalent hydrocarbon radical containingfrom two to ten carbon atoms and at least one carbon-carbon double bond,for example C₂₋₈-alkenyl or C₂₋₆-alkenyl. Typical C₂₋₈-alkenyl groupsand C₂₋₆-alkenyl groups include, but are not limited to, vinyl,1-propenyl, 2-propenyl, iso-propenyl, 1,3-butadienyl, 1-butenyl,2-butenyl, 3-butenyl, 2-methyl-1-propenyl, 1-pentenyl, 2-pentenyl,3-pentenyl, 4-pentenyl, 3-methyl-2-butenyl, 1-hexenyl, 2-hexenyl,3-hexenyl, 2,4-hexadienyl, 5-hexenyl and the like.

The term “alkenylene” as used herein, alone or in combination, refers toa straight or branched chain divalent hydrocarbon radical having fromtwo to ten carbon atoms and at least one carbon-carbon double bond, forexample C₂₋₈-alkenylene or C₂₋₆-alkenylene. Typical C₂₋₈-alkenylenegroups and C₂₋₆-alkenylene groups include, but are not limited to,ethene-1,2-diyl, propene-1,3-diyl, methylene-1,1-diyl, and the like.

The term “alkynyl” as used herein alone or in combination, refers to astraight or branched monovalent hydrocarbon radical containing from twoto ten carbon atoms and at least one triple carbon-carbon bond, forexample C₂₋₈-alkynyl or C₂₋₆-alkynyl. Typical C₂₋₈-alkynyl groups andC₂₋₆-alkynyl groups include, but are not limited to, ethynyl,1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl,2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl,5-hexynyl, 2,4-hexadiynyl and the like.

The term “alkynylene” as used herein alone or in combination, refers toa straight or branched chain divalent hydrocarbon radical having fromtwo to ten carbon atoms and at least one carbon-carbon triple bond, forexample C₂₋₈-alkynylene or C₂₋₆-alkynylene. Typical C₂₋₈-alkynylenegroups and C₂₋₆-alkynylene groups include, but are not limited to,ethyne-1,2-diyl, propyne-1,3-diyl, and the like.

The term “cycloalkyl” as used herein, alone or in combination, refers toa non-aromatic monovalent hydrocarbon radical having from three totwelve carbon atoms, and optionally with one or more degrees ofunsaturation, for example C₃₋₈-cycloalkyl. Such a ring may be optionallyfused to one or more benzene rings or to one or more of other cycloalkylring(s). Typical C₃₋₈-cycloalkyl groups include, but are not limited to,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl,cycloheptyl, cycloheptenyl, cyclooctyl and the like.

The term “cycloalkylene” as used herein, alone or in combination, refersto a non-aromatic carbocyclic divalent hydrocarbon radical having fromthree to twelve carbon atoms and optionally possessing one or moredegrees of unsaturation, for example C₃₋₈-cycloalkylene. Such a ring maybe optionally fused to one or more benzene rings or to one or more ofother cycloalkyl ring(s). Typical C₃₋₈-cycloalkylene groups include, butare not limited to, cyclopropyl-1,1-diyl, cyclopropyl-1,2-diyl,cyclobutyl-1,2-diyl, cyclopentyl-1,3-diyl, cyclohexyl-1,4-diyl,cycloheptyl-1,4-diyl, or cyclooctyl-1,5-diyl, and the like.

The term “heterocyclic” or the term “heterocyclyl” as used herein, aloneor in combination, refers to a three to twelve membered heterocyclicring having one or more degrees of unsaturation containing one or moreheteroatomic substitutions selected from S, SO, SO₂, O, or N, forexample C₃₋₈-heterocyclyl. Such a ring may be optionally fused to one ormore of another “heterocyclic” ring(s) or cycloalkyl ring(s). TypicalC₃₋₈-heterocyclyl groups include, but are not limited to,tetrahydrofuran, 1,4-dioxane, 1,3-dioxane, piperidine, pyrrolidine,morpholine, piperazine, and the like.

The term “heterocyclylene” as used herein, alone or in combination,refers to a three to twelve-membered heterocyclic ring diradicaloptionally having one or more degrees of unsaturation containing one ormore heteroatoms selected from S, SO, SO₂, O, or N. Such a ring may beoptionally fused to one or more benzene rings or to one or more ofanother “heterocyclic” rings or cycloalkyl rings. Examples of“heterocyclylene” include, but are not limited to,tetrahydrofuran-2,5-diyl, morpholine-2,3-diyl, pyran-2,4-diyl,1,4-dioxane-2,3-diyl, 1,3-dioxane-2,4-diyl, piperidine-2,4-diyl,piperidine-1,4-diyl, pyrrolidine-1,3-diyl, morpholine-2,4-diyl,piperazine-1,4-diyl, and the like.

The term “alkoxy” as used herein, alone or in combination, refers to themonovalent radical R^(a)O—, where R^(a) is alkyl as defined above, forexample C₁₋₈-alkyl giving C₁₋₈-alkoxy. Typical C₁₋₈-alkoxy groupsinclude, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy,butoxy, sec-butoxy, tert-butoxy, pentoxy, isopentoxy, hexoxy, isohexoxyand the like.

The term “alkylthio” as used herein, alone or in combination, refers toa straight or branched monovalent radical comprising an alkyl group asdescribed above linked through a divalent sulphur atom having its freevalence bond from the sulphur atom, for example C₁₋₈ alkylthio. TypicalC₁₋₈-alkylthio groups include, but are not limited to, methylthio,ethylthio, propylthio, butylthio, pentylthio, hexylthio and the like.

The term “alkoxycarbonyl” as used herein refers to the monovalentradical R^(a)OC(O)—, where R^(a) is alkyl as described above, forexample C₁₋₈-alkoxycarbonyl. Typical C₁₋₈-alkoxycarbonyl groups include,but are not limited to, methoxycarbonyl, ethoxycarbonyl,propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl,sec-butoxycarbonyl, tertbutoxycarbonyl, 3-methylbutoxycarbonyl,n-hexoxycarbonyl and the like.

The term “carbamoyl” as used herein refers to NH₂C(O)—.

The term “aryl” as used herein refers to a carbocyclic aromatic ringradical or to a aromatic ring system radical. Aryl is also intended toinclude the partially hydrogenated derivatives of the carbocyclicsystems.

The term “heteroaryl”, as used herein, alone or in combination, refersto an aromatic ring radical with for instance 5 to 7 member atoms, or toa aromatic ring system radical with for instance from 7 to 18 memberatoms, containing one or more heteroatoms selected from nitrogen,oxygen, or sulfur heteroatoms, wherein N-oxides and sulfur monoxides andsulfur dioxides are permissible heteroaromatic substitutions; such ase.g. furanyl, thienyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl,triazolyl, tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl,thiadiazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrazinyl,pyrimidinyl, quinolinyl, isoquinolinyl, benzofuranyl, benzothiophenyl,indolyl, and indazolyl, and the like. Heteroaryl is also intended toinclude the partially hydrogenated derivatives of the heterocyclicsystems enumerated below.

Examples of “aryl” and “heteroaryl” includes, but are not limited tophenyl, biphenyl, indene, fluorene, naphthyl (1-naphthyl, 2-naphthyl),anthracene (1-anthracenyl, 2-anthracenyl, 3-anthracenyl), thiophene(2-thienyl, 3-thienyl), furyl (2-furyl, 3-furyl), indolyl, oxadiazolyl,isoxazolyl, thiadiazolyl, oxatriazolyl, thiatriazolyl, quinazolin,fluorenyl, xanthenyl, isoindanyl, benzhydryl, acridinyl, thiazolyl,pyrrolyl (1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl), pyrazolyl (1-pyrazolyl,3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl), imidazolyl (1-imidazolyl,2-imidazolyl, 4-imidazolyl, 5-imidazolyl), triazolyl(1,2,3-triazol-1-yl, 1,2,3-triazol-4-yl, 1,2,3-triazol-5-yl,1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl), oxazolyl (2-oxazolyl,4-oxazolyl, 5-oxazolyl), isooxazolyl (isooxazo-3-yl, isooxazo-4-yl,isooxaz-5-yl), isothiazolyl (isothiazo-3-yl, isothiazo-4-yl,isothiaz-5-yl) thiazolyl (2-thiazolyl, 4-thiazolyl, 5-thiazolyl),pyridyl (2-pyridyl, 3-pyridyl, 4-pyridyl), pyrimidinyl (2-pyrimidinyl,4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl), pyrazinyl, pyridazinyl(3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl), quinolyl (2-quinolyl,3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl),isoquinolyl (1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl,6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl), benzo[b]furanyl(2-benzo[b]furanyl, 3-benzo[b]furanyl, 4-benzo[b]furanyl,5-benzo[b]furanyl, 6-benzo[b]furanyl, 7-benzo[b]furanyl),2,3-dihydro-benzo[b]furanyl (2-(2,3-dihydro-benzo[b]furanyl),3-(2,3-dihydro-benzo[b]furanyl), 4-(2,3-dihydro-benzo[b]furanyl),5-(2,3-dihydro-benzo[b]furanyl), 6-(2,3-dihydro-benzo[b]furanyl),7-(2,3-dihydro-benzo[b]furanyl)), benzo[b]thiophenyl(benzo[b]thiophen-2-yl, benzo[b]thiophen-3-yl, benzo[b]thiophen-4-yl,benzo[b]thiophen-5-yl, benzo[b]thiophen-6-yl, benzo[b]thiophen-7-yl),2,3-dihydro-benzo[b]thiophenyl (2,3-dihydro-benzo[b]thiophen-2-yl,2,3-dihydro-benzo[b]thiophen-3-yl, 2,3-dihydro-benzo[b]thiophen-4-yl,2,3-dihydro-benzo[b]thiophen-5-yl, 2,3-dihydro-benzo[b]thiophen-6-yl,2,3-dihydro-benzo[b]thiophen-7-yl), indolyl (1-indolyl, 2-indolyl,3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl), indazole(1-indazolyl, 3-indazolyl, 4-indazolyl, 5-indazolyl, 6-indazolyl,7-indazolyl), benzimidazolyl (1-benzimidazolyl, 2-benzimidazolyl,4-benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl,8-benzimidazolyl), benzoxazolyl (2-benzoxazolyl, 3-benzoxazolyl,4-benzoxazolyl, 5-benzoxazolyl, 6-benzoxazolyl, 7-benzoxazolyl),benzothiazolyl (2-benzothiazolyl, 4-benzothiazolyl, 5-benzothiazolyl,6-benzothiazolyl, 7-benzothiazolyl), carbazolyl (1-carbazolyl,2-carbazolyl, 3-carbazolyl, 4-carbazolyl), 5H-dibenz[b,f]azepine(5H-dibenz[b,f]azepin-1-yl, 5H-dibenz[b,f]azepine-2-yl,5H-dibenz[b,f]azepine-3-yl, 5H-dibenz[b,f]azepine-4-yl,5H-dibenz[b,f]azepine-5-yl), 10,11-dihydro-5H-dibenz[b,f]azepine(10,11-dihydro-5H-dibenz[b,f]azepine-1-yl,10,11-dihydro-5H-dibenz[b,f]azepine-2-yl,10,11-dihydro-5H-dibenz[b,f]azepine-3-yl,10,11-dihydro-5H-dibenz[b,f]azepine-4-yl,10,11-dihydro-5H-dibenz[b,f]azepine-5-yl), benzo[1,3]dioxole(2-benzo[1,3]dioxole, 4-benzo[1,3]dioxole, 5-benzo[1,3]dioxole,6-benzo[1,3]dioxole, 7-benzo[1,3]dioxole), purinyl, and tetrazolyl(5-tetrazolyl, N-tetrazolyl).

The present invention also relates to partly or fully saturatedanalogues of the ring systems mentioned above.

When two such terms are used in combination, such as in aryl-alkyl-,heteroaryl-alkyl-, cycloalkyl-C₁₋₆-alkyl- and the like, it is to beunderstood that the first mentioned radical is a substituent on thelatter mentioned radical, where the point of substitution is on thelatter of the radicals, for example

The term “arylene”, as used herein, alone or in combination, refers tocarbocyclic aromatic ring diradical or to a aromatic ring systemdiradical. Examples of “arylene” include, but are not limited to,benzene-1,4-diyl, naphthalene-1,8-diyl, and the like. The term “arylene”alone or in combination also include other divalent radicals of themonovalent radicals mentioned in the definition of aryl.

The term “heteroarylene”, as used herein, alone or in combination,refers to a five to seven membered aromatic ring diradical, or to aaromatic ring system diradical, containing one or more heteroatomsselected from nitrogen, oxygen, or sulfur heteroatoms, wherein N-oxidesand sulfur monoxides and sulfur dioxides are permissible heteroaromaticsubstitutions. Examples of “heteroarylene” used herein arefuran-2,5-diyl, thiophene-2,4-diyl, 1,3,4-oxadiazole-2,5-diyl,1,3,4-thiadiazole-2,5-diyl, 1,3-thiazole-2,4-diyl,1,3-thiazole-2,5-diyl, pyridine-2,4-diyl, pyridine-2,3-diyl,pyridine-2,5-diyl, pyrimidine-2,4-diyl, quinoline-2,3-diyl, and thelike. The term “heteroarylene” alone or in combination also includeother divalent radicals of the monovalent radicals mentioned in thedefinition of heteroaryl.

As used herein, the term “fused cycloalkylaryl” refers to a cycloalkylgroup fused to an aryl group, the two having two atoms in common, andwherein the aryl group is the point of substitution. Examples of “fusedcycloalkylaryl” used herein include 5-indanyl,5,6,7,8-tetrahydro-2-naphthyl,

and the like.

As used herein, the term “fused cycloalkylarylene” refers to a fusedcycloalkylaryl, wherein the aryl group is divalent. Examples include

and the like.

As used herein, the term “fused arylcycloalkyl” refers to an aryl groupfused to a cycloalkyl group, the two having two atoms in common, andwherein the cycloalkyl group is the point of substitution Examples of“fused arylcycloalkyl” used herein include 1-indanyl, 2-indanyl,1-(1,2,3,4-tetrahydronaphthyl),

and the like.

As used herein, the term “fused arylcycloalkylene” refers to a fusedarylcycloalkyl, wherein the cycloalkyl group is divalent. Examplesinclude

and the like.

As used herein, the term “fused heterocyclylaryl” refers to aheterocyclyl group fused to an aryl group, the two having two atoms incommon, and wherein the aryl group is the point of substitution.Examples of “fused heterocyclylaryl” used herein include3,4-methylenedioxy-1-phenyl,

and the like

As used herein, the term “fused heterocyclylarylene” refers to a fusedheterocyclylaryl, wherein the aryl group is divalent. Examples include

and the like.

As used herein, the term “fused arylheterocyclyl” refers to an arylgroup fused to a heterocyclyl group, the two having two atoms in common,and wherein the heterocyclyl group is the point of substitution.Examples of “fused arylheterocyclyl” used herein include2-(1,3-benzodioxolyl),

and the like.

As used herein, the term “fused arylheterocyclylene” refers to a fusedarylheterocyclyl, wherein the heterocyclyl group is divalent. Examplesinclude

and the like.

As used herein, the term “fused cycloalkylheteroaryl” refers to acycloalkyl group fused to a heteroaryl group, the two having two atomsin common, and wherein the heteroaryl group is the point ofsubstitution. Examples of “fused cycloalkylheteroaryl” used hereininclude 5-aza-6-indanyl,

-   4,5,6,7-tetrahydro-benzothiazole-2-yl,-   5,6-dihydro-4-H-cyclopentathiazole-2-yl,    and the like.

As used herein, the term “fused heteroarylcycloalkylene” refers to afused heteroarylcycloalkyl, wherein the cycloalkyl group is divalent.Examples include

and the like.

As used herein, the term “fused heterocyclylheteroaryl” refers to aheterocyclyl group fused to a heteroaryl group, the two having two atomsin common, and wherein the heteroaryl group is the point ofsubstitution. Examples of “fused heterocyclylheteroaryl” used hereininclude 1,2,3,4-tetrahydro-beta-carbolin-8-yl,

and the like.

As used herein, the term “fused heterocyclylheteroarylene” refers to afused heterocyclylheteroaryl, wherein the heteroaryl group is divalent.Examples include

and the like.

As used herein, the term “fused heteroarylheterocyclyl” refers to aheteroaryl group fused to a heterocyclyl group, the two having two atomsin common, and wherein the heterocyclyl group is the point ofsubstitution. Examples of “fused heteroarylheterocyclyl” used hereininclude 5-aza-2,3-dihydrobenzofuran-2-yl,

and the like.

As used herein, the term “fused heteroarylheterocyclylene” refers to afused heteroarylheterocyclyl, wherein the heterocyclyl group isdivalent. Examples include

and the like.

The term “alkylsulfanyl”, as used herein, refers to the group R^(a)S—,where R^(a) is alkyl as described above.

The term “alkylsulfenyl”, as used herein, refers to the groupR^(a)S(O)—, where R^(a) is alkyl as described above.

The term “alkylsulfonyl”, as used herein, refers to the group R^(a)SO₂—,where R^(a) is alkyl as described above.

The term “acyl”, as used herein, refers to the group R^(a)C(O)—, whereR^(a) is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, orheterocyclyl as described above.

The term “aroyl”, as used herein, refers to the group R^(a)C(O)—, whereR^(a) is aryl as described above.

The term “heteroaroyl”, as used herein, refers to the group R^(a)C(O)—,where R^(a) is heteroaryl as described above.

The term “aryloxycarbonyl”, as used herein, refers to the groupR^(a)—O—C(O)—, where R^(a) is aryl as described above.

The term “acyloxy”, as used herein, refers to the group R^(a)C(O)O—,where R^(a) is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, orheterocyclyl as described above.

The term “aryloxy”, as used herein refers to the group R^(a)—O—, whereR^(a) is aryl as described above.

The term “aroyloxy”, as used herein, refers to the group R^(a)C(O)O—,where R^(a) is aryl as described above.

The term “heteroaroyloxy”, as used herein, refers to the groupR^(a)C(O)O—, where R^(a) is heteroaryl as described above.

Whenever the terms “alkyl”, “cycloalkyl”, “aryl”, “heteroaryl” or thelike or either of their prefix roots appear in a name of a substituent(e.g. arylalkoxyaryloxy) they shall be interpreted as including thoselimitations given above for “alkyl” and “aryl”.

As used herein, the term “oxo” shall refer to the substituent ═O.

As used herein, the term “mercapto” shall refer to the substituent —SH.

As used herein, the term “carboxy” shall refer to the substituent —COOH.

As used herein, the term “cyano” shall refer to the substituent —CN.

As used herein, the term “aminosulfonyl” shall refer to the substituent—SO₂NH₂.

As used herein, the term “sulfanyl” shall refer to the substituent —S—.

As used herein, the term “sulfenyl” shall refer to the substituent—S(O)—.

As used herein, the term “sulfonyl” shall refer to the substituent—S(O)₂—.

As used herein, the term “direct bond”, where part of a structuralvariable specification, refers to the direct joining of the substituentsflanking (preceding and succeeding) the variable taken as a “directbond”.

The term “lower”, as used herein, refers to an group having between oneand six carbons, and may be indicated with the prefix C_(x-6)—. Loweralkyl may thus be indicated as C₁₋₆-alkyl, while lower alkylene may beindicated as C₂₋₆-alkylene.

A radical such as C_(x-y)-cycloalkyl-C_(a-b)-alkenyl shall designatethat the radical's point of attachment is in part of the radicalmentioned last.

As used herein, the term “optionally” means that the subsequentlydescribed event(s) may or may not occur, and includes both event(s)which occur and events that do not occur.

As used herein, the term “substituted” refers to substitution with thenamed substituent or substituents, multiple degrees of substitutionbeing allowed unless otherwise stated.

As used herein, the terms “contain” or “containing” can refer to in-linesubstitutions at any position along the above defined alkyl, alkenyl,alkynyl or cycloalkyl substituents with one or more of any of O, S, SO,SO₂, N, or N-alkyl, including, for example, —CH₂—O—CH₂—, —CH₂—SO₂—CH₂—,—CH₂—NH—CH₃ and so forth.

Certain of the above defined terms may occur more than once in thestructural formulae, and upon such occurrence each term shall be definedindependently of the other.

As used herein, the term “solvate” is a complex of variablestoichiometry formed by a solute (in this invention, a compound offormula (I)) and a solvent. Such solvents for the purpose of the presentinvention may not interfere with the biological activity of the solute.Solvents may be, by way of example, water, ethanol, or acetic acid.

As used herein, the term “biohydrolyzable ester” is an ester of a drugsubstance (in this invention, a compound of formula (I)) which either a)does not interfere with the biological activity of the parent substancebut confers on that substance advantageous properties in vivo such asduration of action, onset of action, and the like, or b) is biologicallyinactive but is readily converted in vivo by the subject to thebiologically active principle. The advantage is that, for example, thebiohydrolyzable ester is orally absorbed from the gut and is transformedto (I) in plasma. Many examples of such are known in the art and includeby way of example lower alkyl esters (e.g., C₁₋₄), lower acyloxyalkylesters, lower alkoxyacyloxyalkyl esters, alkoxyacyloxy esters, alkylacylamino alkyl esters, and choline esters.

As used herein, the term “biohydrolyzable amide” is an amide of a drugsubstance (in this invention, a compound of general formula (I)) whicheither a) does not interfere with the biological activity of the parentsubstance but confers on that substance advantageous properties in vivosuch as duration of action, onset of action, and the like, or b) isbiologically inactive but is readily converted in vivo by the subject tothe biologically active principle. The advantage is that, for example,the biohydrolyzable amide is orally absorbed from the gut and istransformed to (I) in plasma. Many examples of such are known in the artand include by way of example lower alkyl amides, α-amino acid amides,alkoxyacyl amides, and alkylaminoalkylcarbonyl amides.

As used herein, the term “prodrug” includes biohydrolyzable amides andbiohydrolyzable esters and also encompasses a) compounds in which thebiohydrolyzable functionality in such a prodrug is encompassed in thecompound of formula (I) and b) compounds which may be oxidized orreduced biologically at a given functional group to yield drugsubstances of formula (I). Examples of these functional groups include,but are not limited to, 1,4-dihydropyridine,N-alkylcarbonyl-1,4-dihydropyridine, 1,4-cyclohexadiene, tert-butyl, andthe like.

The term “pharmacologically effective amount” or shall mean that amountof a drug or pharmaceutical agent that will elicit the biological ormedical response of a tissue, animal or human that is being sought by aresearcher or clinician. This amount can be a therapeutically effectiveamount. The term “therapeutically effective amount” shall mean thatamount of a drug or pharmaceutical agent that will elicit thetherapeutic response of an animal or human that is being sought.

The term “treatment” and “treating” as used herein means the managementand care of a patient for the purpose of combating a disease, disorderor condition. The term is intended to include the full spectrum oftreatments for a given disorder from which the patient is suffering,such as the delaying of the progression of the disease, disorder orcondition, the alleviation or relief of symptoms and complications, theprevention of the disease and/or the cure or elimination of the disease,disorder or condition. The patient to be treated is preferably a mammal,in particular a human being.

The term “human insulin” as used herein refers to naturally producedinsulin or recombinantly produced insulin. Recombinant human insulin maybe produced in any suitable host cell, for example the host cells may bebacterial, fungal (including yeast), insect, animal or plant cells.

The expression “insulin derivative” as used herein (and relatedexpressions) refers to human insulin or an analogue thereof in which atleast one organic substituent is bound to one or more of the aminoacids.

By “analogue of human insulin” as used herein (and related expressions)is meant human insulin in which one or more amino acids have beendeleted and/or replaced by other amino acids, including non-codeableamino acids, or human insulin comprising additional amino acids, i.e.more than 51 amino acids, such that the resulting analogue possessesinsulin activity.

DETAILED DESCRIPTION OF THE INVENTION

Glucokinase (GK) plays an essential role in blood glucose homeostasis.GK catalyses glucose phosphorylation, and is the rate-limiting reactionfor glycolysis in hepatocytes and pancreatic β-cells. In liver GKdetermine the rates of both glucose uptake and glycogen synthesis, andit is also thought to be essential for the regulation of variousglucose-responsive genes (Girard, J. et al., Annu Rev Nutr 17, 325-352(1997)). In the β-cells, GK determines glucose utilization and thus isnecessary for glucose-stimulated insulin secretion. GK is also expressedin a population of neurones in the hypothalamus where it might beinvolved in feeding behaviour, and in the gut where it might contributeto the secretion of enteroincretins.

GK has two main distinctive characteristics: its expression, which islimited to tissues that require glucose-sensing (mainly liver andpancreatic β-cells), and its S_(0.5) for glucose, which is much higher(8-12 mM) than that of the other members of the hexokinase family. Dueto these kinetic characteristics, changes in serum glucose levels areparalleled by changes in glucose metabolism in liver which in turnregulate the balance between hepatic glucose output and glucoseconsumption.

Activators of glucokinase may thus be useful for treating diseases whereincreasing the activity of glucokinase is beneficial. Thus, there is aneed for agents which activate glucokinase and increase glucokinaseenzymatic activity. Such agents would be useful for the treatment oftype I diabetes and type II diabetes.

Activators of glucokinase may also play a role in sensing low glucoselevels and generating neurohumoral responses to hypoglycemia and maythus be useful for treating those patients with type 1 diabetes, whichhave a higher-tendency to suffer from hypoglycemia.

Type I diabetes mellitus is a complex disease characterized by anelevated blood glucose concentration and polyuria. Secondary to thepersistent elevation in blood glucose, patients develop devastatingcomplications such as retinopathy, nephropathy, neuropathy, andcardiovascular disease. A major goal to improve the diabetic phenotypeis to reduce fasting and postprandial hyperglycemia and, thus, avoid ordelay the onset of diabetic complications. The Diabetes Control andComplications Trial has indicated that tight glycemic control throughadministration of daily multiple insulin injections delays the onset ofcomplications. However, such intensive therapy is associated with anincrease in body weight and higher risk for development of hypoglycaemicevents. Alternative treatments to achieve glucose control without theseside effects are, therefore, being developed. The combination of GKoverexpression in the liver and subcutaneous insulin injections providesbetter glycemic control in type 1 diabetic animals than treatment withinsulin alone (Morral, N., et al. Human Gene Therapy 13, 1561-1570(2002)). Moreover, overexpression of hepatic GK can compensate, in part,for the metabolic disorders developed by insulin receptor-deficient mice(Jackerott, M. et al. Diabetologia 45, 1292-1297 (2002)).

The present invention also relates to the use of a GK activator for thecombined treatment of diabetes and obesity. GK, the GK regulatoryprotein and the KATP channel are expressed in neurones of thehypothalamus, a region of the brain that is important in the regulationof energy balance and the control of food intake. These neurones havebeen shown to express orectic and anorectic neuropeptides and have beenassumed to be the glucose-sensing neurones within the hypothalamus thatare either inhibited or excited by changes in ambient glucoseconcentrations (Mobbs, C. V. et al, American Journal of Physiology,Endocrinology & Metabolism 281, E649-54 (2001)). The ability of theseneurones to sense changes in glucose levels is defective in a variety ofgenetic and experimentally induced models of obesity (Spanswick, D. etal, Nature Neuroscience 3, 757-8 (2000), Levin, B. E. et al, BrainResearch 808, 317-9 (1998)). Intracerebroventricular (icv) infusion ofglucose analogues, which are competitive inhibitors of glucokinase,stimulate food intake in lean rats (Kurata, K. et al, Metabolism:Clinical & Experimental 38, 46-51 (1989)). In contrast, icv infusion ofglucose suppresses feeding (Kurata, K. et al, Physiology & Behavior 37,615-20 (1986)). Small molecule activators of GK may thus decrease foodintake and weight gain through central effects on GK. Therefore, GKactivators may be of therapeutic use in treating eating disorders,including obesity, in addition to diabetes. The hypothalamic effectswill be additive or synergistic to the effects of the same compoundsacting in the liver and/or pancreas in normalising glucose homeostasis,for the treatment of type 2 diabetes. Thus the GK/GK regulatory proteinsystem can be described as a potential target of benefit in bothdiabetes and obesity.

The amplitude of glucose-induce insulin release is highly dependent onthe action of the gastrointestinal hormones GLP-1 (glucogen-likepeptide 1) and GIP. Unlike sulfonylureas, which stimulate insulinrelease at low as well as high glucose levels, the action of GLP-1 onβ-cells is glucose dependent (Gromada, J. et al., Pflügers Arch 435,583-594 (1998)). GLP-1 receptor agonist and drugs that slow thedegradation of active GLP-1 are therefore under development as a noveltreatments for type 2 diabetes. An alternative strategy would be toenhance endogenous GLP-1 levels. Of potential interest is thepossibility that the release of GLP-1 and GIP might be regulated byglucokinase-expressing endocrine cells (Jetton, T. L. et al., J. Biol.Chem. 269, 3641-3654 (1994)) and glucose-responsive neurons (Liu, M. etal., J. Neurosci. 19, 10305-10317 (1999)). It has been reported that therelease of GIP by intestinal K-cells is directly controlled by glucose(Kieffer, T. J. et al., Am J Physiol 267, E489-E496 (1994)), and GLP-1secretion from GLUTag cells is triggered by glucose through a mechanismsimilar to that found in β-cells for insulin secretion (Reimann, F. etal, Diabetes 51, 2757-2763 (2002)). Small molecule activators ofglucokinase may thus be used to increase GLP-1 and/or GIP secretion andthus for treatment, modulation, inhibition, decreasion, reduction,arrest or prevention of beta cell degeneration, such as necrosis orapoptosis of β-cells.

The present invention provides ortho-substituted heteroaryl and arylureas or carboxamide or sulfonamide activators of glucokinase.

In a first embodiment, the present invention provides compounds of thegeneral formula (I).

whereinA¹ is selected from the group consisting of arylene, heferoarylene,fused cycloalkylarylene, fused heterocyclylarylene, fusedcycloalkylheteroarylene, or fused heterocyclylheteroarylene; optionallysubstituted with one or more substitutents R²³, R²⁴, R²⁵, R²⁶, and R²⁷,wherein

-   -   R²³, R²⁴, R²⁵, R²⁶, and R²⁷ independently of each other are        selected from the group consisting of    -   halogen, —C(O)OR², —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³,        C₁₋₆-alkyl-Z-, C₂₋₆-alkenyl-Z-, C₂₋₆-alkynyl-Z-, cycloalkyl-Z-,        heterocyclyl-Z-, aryl-Z-, heteroaryl-Z-, aryl-C₁₋₆-alkylene-Z-,        heteroaryl-C₁₋₆-alkylene-Z-, heterocyclyl-C₁₋₆-alkylene-Z-,        cycloalkyl-C₁₋₆-alkylene-Z-, N(R⁴R⁵)—C₁₋₆-alkylene-Z-, R⁶—W¹-Z-,        R⁶—W¹—N(R⁴)-Z-, R⁶—N(R⁴)-Z, and R⁶—W¹—C₁₋₆-alkylene-Z-, wherein        -   R² and R³ independently of each other are hydrogen,            C₁₋₆-alkyl, aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-,            C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-, heteroaryl,            or aryl;        -   or        -   R² and R³, when attached to the same nitrogen atom, together            with said nitrogen atom may form a 3 to 8 membered            heterocyclic ring optionally containing one or two further            heteroatoms selected from nitrogen, oxygen and sulfur, and            optionally containing one or two double bonds;        -   Z and W′ independently of each other are a direct bond, —O—,            —N(R⁷)—, —S—, —SO₂—, —C(O)N(R⁷)—, —N(R⁷)C(O)—,            —N(R⁷)CON(R⁸)—, —N(R⁷)SO₂—, —SO₂N(R⁷)—, —C(O)—O—,            —N(R⁷)SO₂N(R⁸)—, or —O—C(O)—, wherein            -   R⁷ and R⁸ in each individual case independently of each                other are hydrogen or alkyl; and        -   R⁴, R⁵, and R⁶ independently of each other are selected from            the group consisting of hydrogen, aryl, alkyl,            heteroaryl-alkylene-, and aryl-alkylene-;        -   or        -   R⁴ and R⁵ may be taken together to form a ring having the            formula —(CH₂)_(j)-Q-(CH₂)_(k)— bonded to the nitrogen atom            to which R⁴ and R⁵ are attached, wherein            -   j and k independently of each other is 1, 2, 3, or 4;                and            -   Q is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—,                —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —NHSO₂—, —SO₂NH—,                —C(O)—O—, —O—C(O)—, —NHSO₂NH—,            -   wherein                -   R⁹ and R¹⁰ independently of each other are selected                    from the group consisting of hydrogen, aryl, alkyl,                    and aryl-alkylene-;                    L¹ is -D-alkylene-E-, -D-alkenylene-E-,                    -D-alkynylene-E-, -D-cycloalkylene-E-,                    -D-heterocyclylene-E-, —O—, —S—, —S(O)—, —S(O)₂—,                    —C(O)—, —N(R¹¹)—, or —C(═N—OR¹²)—, wherein    -   D and E independently of each other are a direct bond, —O— or        —S—;    -   R¹¹ is selected from hydrogen, alkyl, aryl, carbamoyl,        aryl-alkylene-, heteroaryl-alkylene-, alkyl-O—C(O)—,        aryl-alkylene-O—C(O)—, heteroaryl-alkylene-O—C(O)—,        alkyl-NH—C(O)—, aryl-alkylene-NH—C(O)—,        heteroaryl-alkylene-NH—C(O)—, alkyl-SO₂—, aryl-alkylene-SO₂—,        heteroaryl-alkylene-SO₂—, aryl-SO₂—, heteroaryl-SO₂—,        alkyl-NH—SO₂—, aryl-alkylene-NH—SO₂—,        heteroaryl-alkylene-NH—SO₂—, alkyl-C(O)—, aryl-alkylene-C(O)—,        heteroaryl-alkylene-C(O)—, alkyl-Y—, aryl-Y—, heteroaryl-Y—,        aryl-alkylene-Y—, heteroaryl-alkylene-Y—,        N(R¹³)(R¹⁴)-alkylene-Y—, and R¹⁵—W²-alkylene-Y—, wherein        -   Y and W² independently of each other are a direct bond,            —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or —O—C(O)—;        -   R¹³ and R¹⁴ independently of each other are selected from            hydrogen, aryl, heteroaryl, C₁₋₆-alkyl, C₁₋₆-alkoxy,            aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-,            aryl-C₁₋₆-alkoxy-, heteroaryl-C₁₋₆-alkoxy-,            C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,            C₁₋₆-alkoxy-heteroarylene-, or C₁₋₆-alkoxy-arylene-;        -   or        -   R₁₃ and R₁₄ may be taken together to form a ring having the            formula —(CH₂)_(o)—X—(CH₂)_(p)— bonded to the nitrogen atom            to which R₁₃ and R₁₄ are attached, wherein            -   o and p are independently of each other are 1, 2, 3, or                4; and            -   X is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—,                —CON(H)—, —NHC(O)—, —NHCON(H)—, —NHSO₂—, —SO₂N(H)—,                —C(O)—O—, —O—C(O)—, —NHSO₂NH—,            -   wherein                -   R¹⁶ and R¹⁷ are selected from hydrogen, aryl,                    heteroaryl, C₁₋₆-alkyl, C₁₋₆-alkoxy,                    aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-,                    C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,                    C₁₋₆-alkoxy-arylene-, C₁₋₆-alkoxy-heteroarylene-,                    heteroarylaryl-C₁₋₆-alkoxy-, or aryl-C₁₋₆-alkoxy-;                    and        -   R¹⁵ is selected from the group consisting of aryl,            heteroaryl, cycloalkyl, heterocyclyl, alkyl,            heteroaryl-alkylene-, or aryl-alkylene-; and    -   R¹² is selected from hydrogen, aryl, heteroaryl, alkyl,        aryl-alkylene-, heteroaryl-alkylene-, alkyl-arylene-,        alkyl-heteroarylene-, alkoxy-heteroarylene-, or alkoxy-arylene-;        G¹ is alkyl, alkenyl, alkynyl, cycloalkyl or heterocyclyl,        optionally substituted with one or more substituents selected        from the group consisting of —CN, —CF₃, —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹,        C₃₋₁₀-cycloalkyl and C₁₋₆-alkyl, wherein    -   R¹⁸ and R¹⁹ independently of each other are hydrogen,        C₁₋₆-alkyl, heteroaryl-C₁₋₆-alkylene-, aryl-C₁₋₆-alkylene-,        C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-, heteroaryl, or        aryl;    -   or    -   R¹⁸ and R¹⁹, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds;        or        G¹ is aryl, heteroaryl, fused cycloalkylheteroaryl, fused        heterocyclylaryl, or fused cycloalkylaryl,        optionally substituted with one or more substituents R⁴⁰, R⁴¹,        and R⁴²;        L² is a direct bond, alkylene, alkenylene, alkynylene, —N(R²⁰)—,        -alkylene-N(R²⁰)—, -alkenylene-N(R²⁰)—, -alkynylene-N(R²⁰)—,        wherein    -   R²⁰ is hydrogen, or    -   R²⁰ is alkyl, alkenyl, alkynyl, cycloalkyl-W³—,        heterocyclyl-W³—, aryl-W³—, heteroaryl-W³—, optionally        substituted with one or more substituents R³⁰, R³¹, and R³²,        wherein        -   W³ is alkylene or a direct bond;            wherein L¹ and L² are attached to adjacent atoms in A¹;            L³ is —C(O)—, or —S(O)₂—;            R¹ is hydrogen, or            R¹ is alkyl, alkenyl, alkynyl, cycloalkyl-W⁴—,            heterocyclyl-W⁴—, aryl-W⁴—, or heteroaryl-W⁴—, optionally            substituted with one or more substituents R³³, R³⁴, and R³⁵            wherein    -   W⁴ is alkylene or a direct bond;        G² is heteroaryl, fused heterocyclylheteroaryl, or fused        cycloalkylheteroaryl, optionally substituted with one or more        substituents R⁴³, R⁴⁴, and R⁴⁵, wherein said heteroaryl group        possesses a nitrogen atom adjacent to the atom joining said        heteroaryl group to —N(R¹)—;        or a group of the formula        wherein    -   G³ and G⁵ independently of each other are alkyl, alkenyl,        alkynyl, cycloalkyl-R²²—, heterocyclyl-R²²—, aryl-R²²—,        heteroaryl-R²²—;    -   optionally substituted with one or more substituents R⁴⁶, R⁴⁷,        and R⁴⁸, wherein        -   R²² is alkylene or a direct bond; and    -   R²¹ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl-W⁵—, or        heterocyclyl-W⁵—, optionally substituted with one or more        substituents R³⁶, R³⁷, and R³⁸, or R²¹ is aryl-W⁵—, or        heteroaryl-W⁵—, optionally substituted with one or more        substituents R⁴⁹, R⁵⁰, and R⁵¹, wherein    -   W⁵ is alkylene or a direct bond;        wherein        R³⁰, R³¹, R³², R³³, R³⁴, R³⁵, R³⁶, R³⁷, and R³⁸ independently of        each other are selected from        —CHF₂, —CF₃, —OCF₃, —OCHF₂, —OCH₂CF₃, —OCF₂CHF₂, —S(O)₂CF₃,        —SCF₃, —OR⁵², —NR⁵²R⁵³, —SR₅₂, —NR⁵²S(O)₂R⁵³, —S(O)₂NR⁵²R⁵³,        —S(O)NR⁵²R⁵³, —S(O)R⁵², —S(O)₂R⁵², —C(O)NR⁵²R⁵³, —OC(O)NR⁵²R⁵³,        —NR⁵²C(O)R⁵³, —CH₂C(O)NR⁵²R⁵³, —OCH₂C(O)NR⁵²R⁵³, —CH₂OR⁵²,        —CH₂NR⁵²R⁵³, —OC(O)R⁵², —C(O)R⁵² and —C(O)OR⁵²; or        C₂₋₆-alkenyl and C₂₋₆-alkynyl, which may optionally be        substituted with one or more substituents selected from —CN,        —CF₃, —OCF₃, —OR⁵², —NR⁵²R⁵³ and C₁₋₆-alkyl; or        C₃₋₁₀-cycloalkyl, C₄₋₈-cycloalkenyl, heterocyclyl,        C₃₋₁₀-cycloalkyl-C₁₋₆-alkylene-, C₃₋₁₀-cycloalkyl-C₁₋₆-alkoxy-,        C₃₋₁₀-cycloalkyloxy, C₃₋₁₀-cycloalkyl-C₁₋₆-alkylthio-,        C₃₋₁₀-cycloalkylthio, C₃₋₁₀-cycloalkyl-C₂₋₆-alkenylene-,        C₃₋₁₀-cycloalkyl-C₂₋₆-alkynylene-,        C₄₋₈-cycloalkenyl-C₁₋₆-alkylene-,        C₄₋₈-cycloalkenyl-C₂₋₆-alkenylene-,        C₄₋₈-cycloalkenyl-C₂₋₆-alkynylene-, heterocyclyl-C₁₋₆-alkylene-,        heterocyclyl-C₂₋₆-alkenylene-, heterocyclyl-C₂₋₆-alkynylene-,        aryl, aryloxy, aryloxycarbonyl, aroyl, aryl-C₁₋₆-alkoxy-,        aryl-C₁₋₆-alkylene-, aryl-C₂₋₅-alkenylene-,        aryl-C₂₋₆-alkynylene-, heteroaryl, heteroaryl-C₁₋₆-alkylene-,        heteroaryl-C₂₋₆-alkenylene- and heteroaryl-C₂₋₆-alkynylene-, of        which the aryl and heteroaryl moieties optionally may be        substituted with one or more substituents selected from halogen,        —C(O)OR⁵², —CN, —CF₃, —OCF₃, —NO₂, —OR⁵², —NR⁵²R⁵³ and        C₁₋₆-alkyl, wherein    -   R⁵² and R⁵³ independently of each other are hydrogen,        C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene-heteroaryl-C₁₋₆-alkylene-heteroaryl, or aryl;    -   or    -   R⁵² and R⁵³, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds;        R⁴⁰, R⁴¹, R⁴², R⁴³, R⁴⁴, R⁴⁵, R⁴⁶, R⁴⁷, R⁴⁸, R⁴⁹, R⁵⁰ and R⁵¹        independently of each other are        halogen, —CN, —NO₂, C₁₋₆-alkyl, —CHF₂, —CF₃, —OCF₃, —OCHF₂,        —OCH₂CF₃, —OCF₂CHF₂, —S(O)₂CF₃, —SCF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵, —SR⁵⁴,        —NR⁵⁴S(O)₂R⁵⁵, —S(O)₂NR⁵⁴R⁵⁵, —S(O)NR⁵⁴R⁵⁵, —S(O)R⁵⁴, —S(O)₂R⁵⁴,        —C(O)NR⁵⁴R⁵⁵, —OC(O)NR⁵⁴R⁵⁵, —NR⁵⁴C(O)R⁵⁵, —CH₂C(O)NR⁵⁴R⁵⁵,        —CH₂C(O)OR⁵⁴, —OCH₂C(O)NR⁵⁴R⁵⁵, —CH₂OR⁵⁴, —CH₂NR⁵⁴R⁵⁵,        —OC(O)R⁵⁴, —C(O)R⁵⁴ and —C(O)OR⁵⁴; or        C₂₋₆-alkenyl and C₂₋₆-alkynyl, which may optionally be        substituted with one or more substituents selected from —CN,        —CF₃, —OCF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵ and C₁₋₆-alkyl; C₃₋₁₀-cycloalkyl,        C₄₋₈-cycloalkenyl, heterocyclyl,        C₃₋₁₀-cycloalkyl-C₁₋₆-alkylene-, C₃₋₁₀--cycloalkyl-C₁₋₆-alkoxy-,        C₃₋₁₀-cycloalkyloxy, C₃₋₁₀-cycloalkyl-C₁₋₆-alkylthio-,        C₃₋₁₀-cycloalkylthio, C₃₋₁₀-cycloalkyl-C₂₋₆-alkenylene-,        C₃₋₁₀-cycloalkyl-C₂₋₆-alkynylene-,        C₄₋₈-cycloalkenyl-C₁₋₆-alkylene-,        C₄₋₈-cycloalkenyl-C₂₋₆-alkenylene-,        C₄₋₈-cycloalkenyl-C₂₋₆-alkynylene-, heterocyclyl-C₁₋₆-alkylene-,        heterocyclyl-C₂₋₆-alkenylene-, heterocyclyl-C₂₋₆-alkynylene-; or        aryl, aryloxy, aryloxycarbonyl, aroyl, aryl-C₁₋₆-alkoxy-,        aryl-C₁₋₆-alkylene-, aryl-C₂₋₆-alkenylene-,        aryl-C₂₋₆-alkynylene-, heteroaryl, heteroaryl-C₁₋₆-alkylene-,        heteroaryl-C₂₋₆-alkenylene- and heteroaryl-C₂₋₆-alkynylene-, of        which the aryl and heteroaryl moieties optionally may be        substituted with one or more substituents selected from halogen,        —C(O)OR⁵⁴, —CN, —CF₃, —OCF₃, —NO₂, —OR⁵⁴, —NR⁵⁴R⁵⁵ or        C₁₋₆-alkyl, wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen,        C₁₋₆-alkyl, C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,        aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-, heteroaryl, or        aryl;    -   or    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen or        —(CHR⁶³)_(u)—(CHR⁶⁴)_(v)-Z, wherein        -   u is 1 or 2;        -   v is 0, 1 or 2;        -   R⁶³ and R⁶⁴ independently of each other are hydrogen,            C₁₋₆-alkyl, C₁₋₆-alkyl-arylene-aryl, hydroxy, hydroxyalkyl,            amino, or aminoalkyl;        -   Z is hydrogen, —O—R⁶⁵, —C(O)O—R⁶⁵, —CONR⁶⁵R⁶⁶, alkylamino,            or dialkylamino, wherein            -   R⁶⁵ and R⁶⁶ independently of each other is hydrogen or                C₁₋₆-alkyl;        -   or        -   Z is a five or six membered ring wherein at least one ring            atom is nitrogen and the remaining ring atoms are either            carbon or oxygen;    -   or    -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds, and optionally        substituted with one or more C₁₋₆-alkyl groups;        or a pharmaceutically acceptable salt, solvate, or prodrug        thereof.

Other embodiments of the present invention are clear from the followinglist of embodiments.

Embodiment 2: A compound according to embodiment 1, wherein

A¹ is arylene or heteroarylene, optionally substituted with one or moresubstitutents R²³, R²⁴, R²⁵, R²⁶, and R²⁷, wherein

-   -   R²³, R²⁴, R²⁵, R²⁶, and R²⁷ independently of each other are        selected from the group consisting of    -   halogen, —C(O)OR², —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³,        C₁₋₆-alkyl-Z-, C₂₋₆-alkenyl-Z-, C₂₋₆-alkynyl-Z-, cycloalkyl-Z-,        heterocyclyl-Z-, aryl-Z-, heteroaryl-Z-, aryl-C₁₋₆-alkylene-Z-,        heteroaryl-C₁₋₆-alkylene-Z-, heterocyclyl-C₁₋₆-alkylene-Z-,        cycloalkyl-C₁₋₆-alkylene-Z-, N(R⁴R⁵)—C₁₋₆-alkylene-Z-, R⁶—W¹-Z-,        R⁶—W¹—N(R⁴)-Z-, R⁶—N(R⁴)-Z, and R⁶—W¹—C₁₋₆-alkylene-Z-, wherein        -   R², R³, R⁴, R⁵, R⁶, Z, and W¹ are as defined for embodiment            1.            Embodiment 3: A compound according to embodiment 2, wherein            A¹ is C₆₋₁₀-arylene or C₄₋₁₀-heteroarylene, optionally            substituted with one or more substitutents R²³, R²⁵, R²⁶,            and R²⁷ wherein    -   R²³, R²⁴, R²⁵, R²⁶, and R²⁷ independently of each other are        selected from the group consisting of    -   halogen, —C(O)OR², —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³,        C₁₋₆-alkyl-Z-, C₂₋₆-alkenyl-Z-, C₂₋₆-alkynyl-Z-, cycloalkyl-Z-,        heterocyclyl-Z-, aryl-Z-, heteroaryl-Z-, aryl-C₁₋₆-alkylene-Z-,        heteroaryl-C₁₋₆-alkylene-Z-, heterocyclyl-C₁₋₆-alkylene-Z-,        cycloalkyl-C₁₋₆-alkylene-Z-, N(R⁴R⁵)—C₁₋₆-alkylene-Z-, R⁶—W¹-Z-,        R⁶—W¹—N(R⁴)-Z-, R⁶—N(R⁴)-Z, and R⁶—W¹—C₁₋₆-alkylene-Z-, wherein        -   R², R³, R⁴, R⁵, R⁶, Z, and W¹ are as defined for embodiment            1.            Embodiment 4: A compound according to any of embodiments 1            to 3, wherein    -   R²³, R²⁴, R²⁵, R²⁶, and R²⁷ independently of each other are        selected from the group consisting of    -   halogen, —C(O)OR², —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³,        C₁₋₆-alkyl-Z-, cycloalkyl-Z-, heterocyclyl-Z-, aryl-Z-, or        heteroaryl-Z-, N(R⁴R⁵)—C₁₋₆-alkylene-Z-, R⁶—W¹-Z-,        R⁶—W¹—N(R⁴)-Z-, R⁶—N(R⁴)-Z, and R⁶—W¹—C₁₋₆-alkylene-Z-, wherein        -   R², R³, R⁴, R⁵, R⁶, Z, and W¹ are as defined for embodiment            1.            Embodiment 5: A compound according to any of embodiments 1            to 7, wherein    -   R⁴, R⁵, and R⁶ independently of each other are selected from the        group consisting of    -   hydrogen, aryl, alkyl, heteroaryl-alkylene-, and aryl-alkylene-.        Embodiment 6: A compound according to embodiment 11, wherein    -   R⁴, R⁵, and R⁶ independently of each other are hydrogen or        alkyl.        Embodiment 7: A compound according to embodiment 12, wherein    -   R⁴, R⁵, and R⁶ are hydrogen.        Embodiment 8: A compound according to any of embodiments 1 to 7,        wherein    -   R⁴ and R⁵ is taken together to form a ring having the formula        —(CH₂)_(j)-Q-(CH₂)_(k)— bonded to the nitrogen atom to which R⁴        and R⁵ are attached, wherein        -   j and k independently of each other is 1, 2, 3, or 4;        -   Q is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—,            —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —NHSO₂—, —SO₂NH—, —C(O)—O—,            —O—C(O)—, —NHSO₂NH—,        -   wherein            -   R⁹ and R¹⁰ independently of each other are selected from                the group consisting of hydrogen, aryl, alkyl, and                arylalkyl-.                Embodiment 9: A compound according to embodiment 14,                wherein    -   Q is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—, —C(O)NH—,        —NHC(O)—, —NHC(O)NH—, —NHSO₂—, —SO₂NH—, —C(O)—O—, —O—C(O)—,        —NHSO₂NH—,    -   wherein        -   R⁹ and R¹⁰ independently of each other are hydrogen or            alkyl.            Embodiment 10: A compound according to embodiment 15,            wherein    -   Q is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—, —C(O)NH—,        —NHC(O)—, —NHC(O)NH—, —NHSO₂—, —SO₂NH—, —C(O)—O—, —O—C(O)—,        —NHSO₂NH—,        Embodiment 11: A compound according to embodiment 16, wherein Q        is a direct bond.        Embodiment 12: A compound according to any of embodiments 1 to        17, wherein    -   W¹ is a direct bond, —O—, —NH—, —S—, —SO₂—, —C(O)NH—, —NHC(O)—,        —N(H)CON(H)—, —N(H)SO₂—, —SO₂N(H)—, —C(O)—O—, —N(H)SO₂N(H)—, or        —O—C(O)—.        Embodiment 13: A compound according to embodiment 18, wherein W¹        is a direct bond, —O—, —S—, or —SO₂—.        Embodiment 14: A compound according to embodiment 19, wherein W¹        is a direct bond.        Embodiment 15: A compound according to embodiment 7, wherein    -   at least one of R²³, R²⁴, R²⁵, R²⁶, and R²⁷ is halogen,        —C(O)OR², —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³, C₁₋₆-alkyl-Z-,        cycloalkyl-Z-, heterocyclyl-Z-, aryl-Z-, or heteroaryl-Z-,        wherein        -   R², R³, and Z are as defined for embodiment 1.            Embodiment 16: A compound according to embodiment 22,            wherein    -   at least one of R²³, R²⁴, R²⁵, R²⁶, and R²⁷ is halogen,        —C(O)OR², —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³, C₁₋₆-alkyl-Z-,        C₃₋₁₀-cycloalkyl-Z-, C₃₋₁₀-heterocyclyl-Z-, C₃₋₁₀-aryl-Z-, or        C₃₋₁₀-heteroaryl-Z-, wherein        -   R², R³, and Z are as defined for embodiment 1.            Embodiment 17: A compound according to embodiment 23,            wherein    -   at least one of R²³, R²⁴, R²⁵, R²⁶, and R²⁷ is halogen,        —C(O)OR², —CN, —NO₂, —OR², —NR²R³, C₃₋₁₀-alkyl-Z-,        C₃₋₁₀-cycloalkyl-Z-, C₃₋₁₀-heterocyclyl-Z-, C₃₋₁₀-aryl-Z-, or        C₃₋₁₀-heteroaryl-Z-, wherein        -   R², R³, and Z are as defined for embodiment 1.            Embodiment 18: A compound according to embodiment 24,            wherein    -   at least one of R²³, R²⁴, R²⁵, R²⁶, and R²⁷ is halogen,        —C(O)OR², —CN, —NO₂, —OR², or —NR²R³, wherein        -   R², R³, and Z are as defined for embodiment 1.            Embodiment 19: A compound according to any of embodiments 1            to 26, wherein    -   R² and R³ independently of each other are hydrogen, C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-,        C₁₋₅-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-, heteroaryl, or        aryl.        Embodiment 20: A compound according to embodiment 27, wherein    -   R² and R³ independently of each other, are hydrogen, C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene- or aryl.        Embodiment 21: A compound according to embodiment 28, wherein    -   R² is hydrogen or C₁₋₆-alkyl.        Embodiment 22: A compound according to embodiment 29, wherein    -   R² is hydrogen.        Embodiment 23: A compound according to any of embodiments 1 to        30, wherein    -   R³ is hydrogen or C₁₋₆-alkyl.        Embodiment 24: A compound according to embodiment 31, wherein    -   R³ is hydrogen.        Embodiment 25: A compound according to any of embodiments 1 to        22, wherein    -   R² and R³, when attached to the same nitrogen atom, together        with said nitrogen atom may form a 3 to 8 membered heterocyclic        ring optionally containing one or two further heteroatoms        selected from nitrogen, oxygen and sulfur, and optionally        containing one or two double bonds.        Embodiment 26: A compound according to any of embodiments 1 to        33, wherein    -   Z is a direct bond, —O—, —NH—, —S—, —SO₂—, —C(O)NH—, —NHC(O)—,        —N(H)CON(H)—, —N(H)SO₂—, —SO₂N(H)—, —C(O)—O—, —N(H)SO₂N(H)—, or        —O—C(O)—.        Embodiment 27: A compound according to embodiment 34, wherein    -   Z is a direct bond, —O—, —S—, or —SO₂—.        Embodiment 28: A compound according to embodiment 35, wherein    -   Z is a direct bond.        Embodiment 29: A compound according to embodiment 2, wherein        A¹ is        R²³, R²⁴, R²⁵, and R²⁶, independently of each other, are        hydrogen or as defined for embodiment 1.        Embodiment 30: A compound according to embodiment 37, wherein    -   R²³, R²⁴, R²⁵, and R²⁶ independently of each other are selected        from the group consisting of    -   halogen, —C(O)OR², —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³,        C₁₋₆-alkyl-Z-, cycloalkyl-Z-, heterocyclyl-Z-, aryl-Z-, or        heteroaryl-Z-, N(R⁴R⁵)—C₁₋₆-alkylene-Z-, R⁶—W¹-Z-,        R⁶—W¹—N(R⁴)-Z-, R⁶—N(R⁴)-Z, and R⁶—W¹—C₁₋₆-alkylene-Z-, wherein        -   R², R³, R⁴, R⁵, R⁶, Z, and W¹ are as defined for embodiment            1.            Embodiment 31: A compound according to embodiment 37 or 38,            wherein    -   R⁴, R⁵, and R⁶ independently of each other are selected from the        group consisting of    -   hydrogen, aryl, alkyl, heteroaryl-alkylene-, and aryl-alkylene-.        Embodiment 32: A compound according to embodiment 39, wherein    -   R⁴, R⁵, and R⁶ independently of each other are hydrogen or        alkyl.        Embodiment 33: A compound according to embodiment 40, wherein    -   R⁴, R⁵, and R⁶ are hydrogen.        Embodiment 34: A compound according to embodiment 37 or 38,        wherein    -   R⁴ and R⁵ is taken together to form a ring having the formula        —(CH₂)_(j)-Q-(CH₂)_(k)— bonded to the nitrogen atom to which R⁴        and R⁵ are attached, wherein        -   j and k independently of each other is 1, 2, 3, or 4;        -   Q is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—,            —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —NHSO₂—, —SO₂NH—, —C(O)—O—,            —O—C(O)—, —NHSO₂NH—,        -   wherein            -   R⁹ and R¹⁰ independently of each other are selected from                the group consisting of hydrogen, aryl, alkyl, and                arylalkyl-.                Embodiment 35: A compound according to embodiment 42,                wherein    -   Q is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—, —C(O)NH—,        —NHC(O)—, —NHC(O)NH—, —NHSO₂—, —SO₂NH—, —C(O)—O—, —O—C(O)—,        —NHSO₂NH—,    -   wherein        -   R⁹ and R¹⁰ independently of each other are hydrogen or            alkyl.            Embodiment 36: A compound according to embodiment 43,            wherein    -   Q is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—, —C(O)NH—,        —NHC(O)—, —NHC(O)NH—, —NHSO₂—, —SO₂NH—, —C(O)—O—, —O—C(O)—,        —NHSO₂NH—,        Embodiment 37: A compound according to embodiment 44, wherein    -   Q is a direct bond.        Embodiment 38: A compound according to any of embodiments 37 to        45, wherein    -   W¹ is a direct bond, —O—, —NH—, —S—, —SO₂—, —C(O)NH—, —NHC(O)—,        —N(H)CON(H)—, —N(H)SO₂—, —SO₂N(H)—, —C(O)—O—, —N(H)SO₂N(H)—, or        —O—C(O)—.        Embodiment 39: A compound according to embodiment 46, wherein    -   W¹ is a direct bond, —O—, —S—, or —SO₂—.        Embodiment 40: A compound according to embodiment 48, wherein    -   W¹ is a direct bond.        Embodiment 41: A compound according to embodiment 37, wherein    -   at least one of R²³, R²⁴, R²⁵, and R²⁶ is halogen, —C(O)OR²,        —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³, C₁₋₆ alkyl-Z-,        cycloalkyl-Z-, heterocyclyl-Z-, aryl-Z-, or heteroaryl-Z-,        wherein        -   R², R³, and Z are as defined for embodiment 37.            Embodiment 42: A compound according to embodiment 50,            wherein    -   at least one of R²³, R²⁴, R²⁵, and R²⁶ is halogen, —C(O)OR²,        —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³, C₁₋₆-alkyl-Z-,        C₃₋₁₀-cycloalkyl-Z-, C₃₋₁₀-heterocyclyl-Z-, C₃₋₁₀-aryl-Z-, or        C₃₋₁₀-heteroaryl-Z-, wherein        -   R², R³, and Z are as defined for embodiment 37.            Embodiment 43: A compound according to embodiment 51,            wherein    -   at least one of R²³, R²⁴, R²⁵, and R²⁶ is halogen, —C(O)OR²,        —CN, —NO₂, —OR², —NR²R³, C₁₋₆-alkyl-Z-, C₃₋₁₀-cycloalkyl-Z-,        C₃₋₁₀-heterocyclyl-Z-, C₃₋₁₀-aryl-Z-, or C₃₋₁₀-heteroaryl-Z-,        wherein        -   R², R³, and Z are as defined for embodiment 37.            Embodiment 44: A compound according to any of embodiments 37            to 52, wherein    -   Z is a direct bond, —O—, —NH—, —S—, —SO₂—, —C(O)NH—, —NHC(O)—,        —N(H)CON(H)—, —N(H)SO₂—, —SO₂N(H)—, —C(O)—O—, —N(H)SO₂N(H)—, or        —O—C(O)—.        Embodiment 45: A compound according to embodiment 53, wherein    -   Z is a direct bond, —O—, —S—, or —SO₂—.        Embodiment 46: A compound according to embodiment 54, wherein    -   Z is a direct bond.        Embodiment 47: A compound according to embodiment 52, wherein    -   at least one of R²³, R²⁴, R²⁵, and R²⁶ is halogen, —C(O)OR²,        —CN, —NO₂, —OR², —NR²R³, or C₁₋₆-alkyl, wherein        -   R², and R³ are as defined for embodiment 37.            Embodiment 48: A compound according to any of embodiments 37            to 56, wherein    -   R² and R³ independently of each other are hydrogen, C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-,        C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-, heteroaryl, or        aryl.        Embodiment 49: A compound according to embodiment 57, wherein    -   R² and R³ independently of each other, are hydrogen, C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene- or aryl.        Embodiment 50: A compound according to embodiment 58, wherein    -   R² is hydrogen or C₁₋₆-alkyl.        Embodiment 51: A compound according to embodiment 59, wherein    -   R² is hydrogen.        Embodiment 52: A compound according to any of embodiments 37 to        60, wherein    -   R³ is hydrogen or C₁₋₆-alkyl.        Embodiment 53: A compound according to embodiment 61, wherein    -   R³ is hydrogen.        Embodiment 54: A compound according to any of embodiments 37 to        50, wherein    -   R² and R³, when attached to the same nitrogen atom, together        with said nitrogen atom may form a 3 to 8 membered heterocyclic        ring optionally containing one or two further heteroatoms        selected from nitrogen, oxygen and sulfur, and optionally        containing one or two double bonds.        Embodiment 55: A compound according to any of embodiments 37 to        55, wherein    -   at least one of R²³, R²⁴, R²⁵, and R²⁶ are hydrogen.        Embodiment 56: A compound according to embodiment 64, wherein    -   at least two of R²³, R²⁴, R²⁵, and R²⁶ are hydrogen.        Embodiment 57. A compound according to claim 65, wherein    -   R²³ and R²⁶ are hydrogen.        Embodiment 58: A compound according to embodiment 65 or claim        66, wherein    -   at least three of R²³, R²⁴, R²⁵, and R²⁶ are hydrogen.        Embodiment 59: A compound according to any of embodiments 37 to        67, wherein R²⁴ or R²⁵ is halogen.        Embodiment 60: A compound according to embodiment 68, wherein        R²⁴ or R²⁵ is fluoro.        Embodiment 61: A compound according to any of embodiments 37 to        67, wherein R²⁴ or R²⁵ is C₁₋₆-alkyl.        Embodiment 62: A compound according to embodiment 68, wherein        R²⁴ or R²⁵ is methyl.        Embodiment 63: A compound according to any of embodiments 37 to        67, wherein    -   R²⁴ is hydrogen.        Embodiment 64: A compound according to any of embodiments 37 to        72, wherein    -   R²⁵ is hydrogen.        Embodiment 65: A compound according to embodiment 37, wherein    -   R²³, R²⁴, R²⁵, and R²⁶ are hydrogen.        Embodiment 66: A compound according to any of embodiments 1 to        74, wherein    -   L¹ is -D-alkylene-E-, —O—, —S—, —S(O)—, —S(O)₂—, —C(O)—,        —N(R¹¹)—, or —C(═N—OR¹²), wherein        -   D, E, R¹¹ and R¹² are as defined for embodiment 1.            Embodiment 67: A compound according to embodiment 75,            wherein    -   L¹ is -D-alkylene-E-, —O—, —C(O)—, —N(R¹¹)—, or —C(═N—OR¹²)—,        wherein        -   D, E, R¹¹ and R¹² are as defined for embodiment 1.            Embodiment 68: A compound according to embodiment 75,            wherein    -   L¹ is —O—.        Embodiment 69. A compound according to embodiment 75, wherein    -   L¹ is —S—.        Embodiment 70: A compound according to embodiment 75, wherein    -   L¹ is —C(O)—.        Embodiment 71: A compound according to any of embodiments 1 to        76, wherein    -   D is a direct bond or —O—;    -   E is a direct bond or —O—; and    -   R¹¹ and R¹² are as defined for embodiment 1.        Embodiment 72: A compound according to embodiment 81, wherein    -   D is a direct bond.        Embodiment 73: A compound according to embodiment 81, wherein    -   D is —O—.        Embodiment 74: A compound according to any of embodiments 81 to        83, wherein    -   E is a direct bond.        Embodiment 75: A compound according to any of embodiments 81 to        83, wherein    -   E is —O—.        Embodiment 76: A compound according to any of embodiments 1 to        85, wherein    -   R¹¹ is selected from hydrogen, alkyl, aryl, carbamoyl,        aryl-alkylene-, alkyl-NH—C(O)—, aryl-alkylene-NH—C(O)—,        alkyl-SO₂—, aryl-alkylene-SO₂—, aryl-SO₂—, SO₂—, alkyl-C(O)—,        aryl-alkylene-C(O)—, N(R¹³)(R¹⁴)-alkylene-Y—, and        R¹⁵—W²-alkylene-Y—, wherein        -   Y and W² independently of each other are a direct bond,            —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or —O—C(O)—;        -   R¹³ and R¹⁴ independently of each other are selected from            hydrogen, aryl, C₁₋₆-alkyl, or aryl-C₁₋₆-alkylene-;        -   or        -   R¹³ and R¹⁴ may be taken together to form a ring having the            formula —(CH₂), —X—(CH₂)_(p)— bonded to the nitrogen atom to            which R¹³ and R¹⁴ are attached, wherein            -   o and p are independently of each other are 1, 2, 3, or                4; and            -   X is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—,                —CON(H)—, —NHC(O)—, —NHCON(H)—, —NHSO₂—, —SO₂N(H)—,                —C(O)—O—, —O—C(O)—, —NHSO₂NH—,            -   wherein                -   R¹⁶ and R¹⁷ are selected from hydrogen, aryl,                    heteroaryl, C₁₋₆-alkyl, C₁₋₆-alkoxy,                    aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-,                    C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,                    C₁₋₆-alkoxy-arylene-, C₁₋₆-alkoxy-heteroarylene-,                    heteroarylaryl-C₁₋₆-alkoxy-, or aryl-C₁₋₆-alkoxy-;                    and    -   R¹⁵ is selected from the group consisting of aryl, heteroaryl,        cycloalkyl, heterocyclyl, alkyl, or aryl-alkylene-.        Embodiment 77: A compound according to embodiment 86, wherein    -   R¹¹ is selected from hydrogen, alkyl, aryl, carbamoyl,        aryl-alkylene-, alkyl-NH—C(O)—, aryl-alkylene-NH—C(O)—,        alkyl-SO₂—, aryl-alkylene-SO₂—, aryl-SO₂—, SO₂—, alkyl-C(O)—,        aryl-alkylene-C(O)—, N(R¹³)(R¹⁴)-alkylene-Y—, and        R¹⁵—W²-alkylene-Y—, wherein        -   Y and W² independently of each other are a direct bond,            —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or —O—C(O)—;        -   R¹³ and R¹⁴ independently of each other are selected from            hydrogen, aryl, C₁₋₆-alkyl, or aryl-C₁₋₆-alkylene-;        -   or        -   R¹³ and R¹⁴ may be taken together to form a ring having the            formula —(CH₂)_(o)—X—(CH₂)_(p)— bonded to the nitrogen atom            to which R¹³ and R¹⁴ are attached, wherein            -   o and p are independently of each other are 1, 2, 3, or                4; and            -   X is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—,                —CON(H)—, —NHC(O)—, —NHCON(H)—, —NHSO₂—, —SO₂N(H)—,                —C(O)—O—, —O—C(O)—, —NHSO₂NH—,            -   wherein                -   R¹⁶ and R¹⁷ are hydrogen; and    -   R¹⁵ is selected from the group consisting of aryl, heteroaryl,        cycloalkyl, heterocyclyl, alkyl, or aryl-alkylene-.        Embodiment 78: A compound according to embodiment 87, wherein    -   R¹¹ is selected from hydrogen, alkyl, aryl, carbamoyl,        aryl-alkylene-, alkyl-NH—C(O)—, aryl-alkylene-NH—C(O)—,        alkyl-SO₂—, aryl-alkylene-SO₂—, aryl-SO₂—, SO₂—, alkyl-C(O)—,        aryl-alkylene-C(O)—, N(R¹³)(R¹⁴)-alkylene-Y—, and        R¹⁵—W²-alkylene-Y—, wherein        -   Y and W² independently of each other are a direct bond,            —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or —O—C(O)—;        -   R¹³ and R¹⁴ independently of each other are selected from            hydrogen, aryl, C₁₋₆-alkyl, or aryl-C₁₋₆-alkylene-;        -   or        -   R¹³ and R¹⁴ may be taken together to form a ring having the            formula —(CH₂)_(o)—X—(CH₂)_(p)— bonded to the nitrogen atom            to which R¹³ and R¹⁴ are attached, wherein            -   and p are independently of each other are 1, 2, 3, or 4;            -   X is a direct bond; and    -   R¹⁵ is selected from the group consisting of aryl, heteroaryl,        cycloalkyl, heterocyclyl, alkyl, or aryl-alkylene-.        Embodiment 79: A compound according to embodiment 88, wherein    -   R¹¹ is selected from hydrogen, alkyl, aryl, carbamoyl,        aryl-alkylene-, alkyl-NH—C(O)—, aryl-alkylene-NH—C(O)—,        alkyl-SO₂—, aryl-alkylene-SO₂—, aryl-SO₂—, SO₂—, alkyl-C(O)—,        aryl-alkylene-C(O)—, N(R¹³)(R¹⁴)-alkylene-Y—, and        R¹⁵—W²-alkylene-Y—, wherein        -   Y and W² independently of each other are a direct bond,            —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or —O—C(O)—;        -   R¹³ and R¹⁴ independently of each other are selected from            hydrogen, aryl, C₁₋₆-alkyl, or aryl-C₁₋₆-alkylene-; and        -   R¹⁵ is selected from the group consisting of aryl,            heteroaryl, cycloalkyl, heterocyclyl, alkyl, or            aryl-alkylene-.            Embodiment 80: A compound according to embodiment 89,            wherein    -   R¹¹ is selected from hydrogen, alkyl, aryl, carbamoyl,        aryl-alkylene-, alkyl-NH—C(O)—, aryl-alkylene-NH—C(O)—,        alkyl-SO₂—, aryl-alkylene-SO₂—, aryl-SO₂—, SO₂—, alkyl-C(O)—,        aryl-alkylene-C(O)—, N(R¹³)(R¹⁴)-alkylene-Y—, and        R¹⁵—W²-alkylene-Y—, wherein        -   Y and W² independently of each other are a direct bond,            —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or —O—C(O)—;        -   R¹³ and R¹⁴ are hydrogen; and        -   R¹⁵ is selected from the group consisting of aryl,            heteroaryl, cycloalkyl, heterocyclyl, alkyl, or            aryl-alkylene-.            Embodiment 81: A compound according to embodiment 90,            wherein    -   R¹¹ is selected from hydrogen, alkyl, aryl, carbamoyl,        aryl-alkylene-, alkyl-NH—C(O)—, aryl-alkylene-NH—C(O)—,        alkyl-SO₂—, aryl-alkylene-SO₂—, aryl-SO₂—, SO₂—, alkyl-C(O)—,        aryl-alkylene-C(O)—, N(R¹³)(R¹⁴)-alkylene-Y—, and        R¹⁵—W²-alkylene-Y—, wherein        -   Y is a direct bond;        -   W² is a direct bond, —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or            —O—C(O)—;        -   R¹³ and R¹⁴ are hydrogen; and        -   R¹⁵ is selected from the group consisting of aryl,            heteroaryl, cycloalkyl, heterocyclyl, alkyl, or            aryl-alkylene-.            Embodiment 82: A compound according to embodiment 90,            wherein    -   R¹¹ is selected from hydrogen, alkyl, aryl, carbamoyl,        aryl-alkylene-, alkyl-NH—C(O)—, aryl-alkylene-NH—C(O)—,        alkyl-SO₂—, aryl-alkylene-SO₂—, aryl-SO₂—, SO₂—, alkyl-C(O)—,        aryl-alkylene-C(O)—, N(R¹³)(R¹⁴)-alkylene-Y—, and        R¹⁵—W²-alkylene-Y—, wherein        -   Y is a direct bond, —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or            —O—C(O)—;        -   W² is a direct bond;        -   R¹³ and R¹⁴ are hydrogen; and        -   R¹⁵ is selected from the group consisting of aryl,            heteroaryl, cycloalkyl, heterocyclyl, alkyl, or            aryl-alkylene-.            Embodiment 83: A compound according to any of embodiments 90            to 92, wherein    -   R¹¹ is selected from hydrogen, alkyl, aryl, carbamoyl,        aryl-alkylene-, alkyl-NH—C(O)—, aryl-alkylene-NH—C(O)—,        alkyl-SO₂—, aryl-alkylene-SO₂—, aryl-SO₂—, SO₂—, alkyl-C(O)—,        aryl-alkylene-C(O)—, NH₂-alkylene-, and R¹⁵-alkylene-, wherein        -   R¹⁵ is selected from the group consisting of aryl,            heteroaryl, cycloalkyl, heterocyclyl, alkyl, or            aryl-alkylene-.            Embodiment 84: A compound according to embodiment 93,            wherein    -   R¹¹ is selected from hydrogen, alkyl, aryl, carbamoyl,        aryl-alkylene-, alkyl-NH—C(O)—, aryl-alkylene-NH—C(O)—,        alkyl-SO₂—, aryl-alkylene-SO₂—, aryl-SO₂—, SO₂—, alkyl-C(O)—,        aryl-alkylene-C(O)—, and NH₂-alkylene-.        Embodiment 85: A compound according to embodiment 94, wherein    -   R¹¹ is hydrogen or alkyl.        Embodiment 86: A compound according to embodiment 95, wherein    -   R¹¹ is hydrogen.        Embodiment 87: A compound according to any of embodiments 1 to        96, wherein    -   R¹² is hydrogen or alkyl.        Embodiment 88: A compound according to embodiment 97, wherein    -   R¹² is hydrogen.        Embodiment 89: A compound according to any of embodiments 1 to        98, wherein    -   G¹ is alkyl, alkenyl, alkynyl, cycloalkyl or heterocyclyl,        optionally substituted with one or more substituents selected        from the group consisting of —CN, —CF₃, —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹,        C₃₋₁₀-cycloalkyl and C₁₋₆-alkyl, wherein        -   R¹⁸ and R¹⁹ are as defined for embodiment 1.            Embodiment 90: A compound according to embodiment 99,            wherein    -   G¹ is alkyl, alkenyl, alkynyl, cycloalkyl or heterocyclyl,        optionally substituted with one or more substituents selected        from the group consisting of —CN, —CF₃, —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹        and C₁₋₆-alkyl, wherein        -   R¹⁸ and R¹⁹ are as defined for embodiment 1.            Embodiment 91: A compound according to embodiment 99,            wherein    -   G¹ is C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl, C₃₋₁₀-cycloalkyl        or C₃₋₁₀-heterocyclyl, optionally substituted with one or more        substituents selected from the group consisting of —CN, —CF₃,        —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹, C₃₋₁₀-cycloalkyl and C₁₋₆-alkyl, wherein        -   R¹⁸ and R¹⁹ are as defined for embodiment 1.            Embodiment 92: A compound according to embodiment 100 or            embodiment 101, wherein    -   G¹ is C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl, C₃₋₁₀-cycloalkyl        or C₃₋₁₀-heterocyclyl, optionally substituted with one or more        substituents selected from the group consisting of —CN, —CF₃,        —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹ and C₁₋₆-alkyl, wherein        -   R¹⁸ and R¹⁹ are as defined for embodiment 1.            Embodiment 93: A compound according to any of embodiments 99            to 102, wherein    -   R¹⁸ and R¹⁹, independently of each other, are hydrogen,        C₁₋₆-alkyl, heteroaryl-C₁₋₆-alkylene-, aryl-C₁₋₆-alkylene-,        C₁₋₅-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-, heteroaryl, or        aryl.        Embodiment 94: A compound according to embodiment 110, wherein    -   R¹⁸ and R¹⁹, independently of each other, are hydrogen,        C₁₋₆-alkyl, C₃₋₁₀-heteroaryl-C₁₋₆-alkylene-,        C₃₋₁₀-aryl-C₁₋₆-alkylene-, C₁₋₆-alkyl-C₃₋₁₀-arylene-,        C₁₋₆-alkyl-C₃₋₁₀-heteroarylene-, C₃₋₁₀-heteroaryl, or        C₃₋₁₀-aryl.        Embodiment 95: A compound according to embodiment 111, wherein    -   R¹⁸ and R¹⁹, independently of each other, are hydrogen or        C₁₋₆-alkyl.        Embodiment 96: A compound according to embodiment 112, wherein    -   R¹⁸ is hydrogen.        Embodiment 97: A compound according to embodiment 112 or 113,        wherein    -   R¹⁹ is hydrogen.        Embodiment 98: A compound according to embodiment 100 or        embodiment 102, wherein    -   R¹⁸ and R¹⁹, when attached to the same nitrogen atom, together        with the said nitrogen atom forms a 3 to 8 membered heterocyclic        ring optionally containing one or two further heteroatoms        selected from nitrogen, oxygen and sulfur, and optionally        containing one or two double bonds.        Embodiment 99: A compound according to any of embodiments 1 to        98, wherein    -   G¹ is alkyl or cycloalkyl, optionally substituted with one or        more substituents selected from the group consisting of —CN,        —CF₃, —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹ and C₁₋₆-alkyl,    -   or G¹ is aryl optionally substituted with one or more        substituents R⁴⁰, R⁴¹, and R⁴²,    -   wherein R¹⁸, R¹⁹, R⁴⁰, R⁴¹, and R⁴² are as defined for        embodiment 1.        Embodiment 100: A compound according to embodiment 116, wherein    -   G¹ is C₁₋₆-alkyl or C₃₋₁₀-cycloalkyl, optionally substituted        with one or more substituents selected from the group consisting        of —CN, —CF₃, —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹ and C₁₋₆-alkyl,    -   or G¹ is C₃₋₁₀-aryl optionally substituted with one or more        substituents R⁴⁰, R⁴¹, and R⁴² wherein R¹⁸, R¹⁹, R⁴⁰, R⁴¹, and        R⁴² are as defined for embodiment 1.        Embodiment 101: A compound according to embodiment 116 or        embodiment 117, wherein    -   R¹⁸ and R¹⁹, independently of each other, are hydrogen,        C₁₋₆-alkyl, heteroaryl-C₁₋₆-alkylene-, aryl-C₁₋₆-alkylene-,        C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-, heteroaryl, or        aryl.        Embodiment 102: A compound according to embodiment 119, wherein    -   R¹⁸ and R¹⁹, independently of each other, are hydrogen,        C₁₋₆-alkyl, C₃₋₁₀-heteroaryl-C₁₋₆-alkylene-,        C₃₋₁₀-aryl-C₁₋₆-alkylene-, C₁₋₆-alkyl-C₃₋₁₀-arylene-,        C₁₋₆-alkyl-C₃₋₁₀-heteroarylene-, C₃₋₁₀-heteroaryl, or        C₃₋₁₀-aryl.        Embodiment 103: A compound according to embodiment 120, wherein    -   R¹⁸ and R¹⁹, independently of each other, are hydrogen or        C₁₋₆-alkyl.        Embodiment 104: A compound according to embodiment 121, wherein    -   R¹⁸ is hydrogen.        Embodiment 105: A compound according to embodiment 121 or 122,        wherein    -   R¹⁹ is hydrogen.        Embodiment 106: A compound according to embodiment 116 or        embodiment 117, wherein    -   R¹⁸ and R¹⁹, when attached to the same nitrogen atom, together        with the said nitrogen atom forms a 3 to 8 membered heterocyclic        ring optionally containing one or two further heteroatoms        selected from nitrogen, oxygen and sulfur, and optionally        containing one or two double bonds.        Embodiment 107: A compound according to any of embodiments 116        to 124, wherein    -   R⁴⁰, R⁴¹, and R⁴² independently of each other are    -   halogen, —CN, —NO₂, C₁₋₆-alkyl, —CHF₂, —CF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵,        —SR⁵⁴, —NR⁵⁴S(O)₂R⁵⁵, —S(O)₂NR⁵⁴R⁵⁵, —S(O)NR⁵⁴R⁵⁵, —S(O)R⁵⁴,        —S(O)₂R⁵⁴, —C(O)NR⁵⁴R⁵⁵, —OC(O)NR⁵⁴R⁵⁵, —NR⁵⁴C(O)R⁵⁵,        —CH₂C(O)NR⁵⁴R⁵⁵, —CH₂C(O)OR⁵⁴, —OCH₂OC(O)NR⁵⁴R⁵⁵, —CH₂OR⁵⁴,        —CH₂NR⁵⁴R⁵⁵, and —C(O)OR⁵⁴; or    -   C₂₋₄-alkenyl and C₂₋₆-alkynyl, which may optionally be        substituted with one or more substituents selected from —CN,        —CF₃, —OCF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵ and C₁₋₆-alkyl, wherein        -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen,            C₁₋₆-alkyl, C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,            aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-, heteroaryl,            or aryl;        -   or        -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom,            together with the said nitrogen atom may form a 3 to 8            membered heterocyclic ring optionally containing one or two            further heteroatoms selected from nitrogen, oxygen and            sulfur, and optionally containing one or two double bonds.            Embodiment 108: A compound according to embodiment 125,            wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen, or        C₁₋₆-alkyl, C₁₋₆-alkyl-C₃₋₁₀-arylene-,        C₁₋₆-alkyl-C₃₋₁₀-heteroarylene-, C₃₋₁₀-aryl-C₁₋₆-alkylene-,        C₃₋₁₀-heteroaryl-C₁₋₆-alkylene-, C₃₋₁₀-heteroaryl, or        C₃₋₁₀-aryl.        Embodiment 109: A compound according to embodiment 128, wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment 110: A compound according to embodiment 129, wherein    -   R⁵⁴ is hydrogen.        Embodiment 111: A compound according to embodiment 129 or        embodiment 130, wherein    -   R⁵⁵ is hydrogen.        Embodiment 112: A compound according to any of embodiments 1 to        98, wherein    -   G¹ is aryl or heteroaryl, optionally substituted with one or        more substituents R⁴⁰, R⁴¹, and R⁴², wherein        -   R⁴⁰, R⁴¹, and R⁴² are as defined for embodiment 1.            Embodiment 113: A compound according to embodiment 133,            wherein    -   G¹ is C₃₋₁₀-aryl or C₃₋₁₀-heteroaryl, optionally substituted        with one or more substituents R⁴⁰, R⁴¹, and R⁴² wherein        -   R⁴⁰, R⁴¹, and R⁴² are as defined for embodiment 1.            Embodiment 114: A compound according to embodiment 133,            wherein    -   G¹ is aryl, optionally substituted with one or more substituents        R⁴⁰, R⁴¹, and R⁴², wherein        -   R⁴⁰, R⁴¹, and R⁴² are as defined for embodiment 1.            Embodiment 115: A compound according to embodiment 135,            wherein    -   G¹ is C₃₋₁₀-aryl, optionally substituted with one or more        substituents R⁴⁰, R⁴¹, and R⁴², wherein        -   R⁴⁰, R⁴¹, and R⁴² are as defined for embodiment 1.            Embodiment 116: A compound according to any of embodiments            133 to 136, wherein    -   R⁴⁰, R⁴¹, and R⁴² independently of each other are    -   halogen, —CN, —NO₂, C₁₋₆-alkyl, —CHF₂, —CF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵,        —SR⁵⁴, —NR⁵⁴S(O)₂R⁵⁵, —S(O)₂NR⁵⁴R⁵⁵, —S(O)NR⁵⁴R⁵⁵, —S(O)R⁵⁴;        —S(O)₂R⁵⁴, —C(O)NR⁵⁴R⁵⁵, —OC(O)NR⁵⁴R⁵⁵, —NR⁵⁴C(O)R⁵⁵,        —CH₂C(O)NR⁵⁴R⁵⁵, —CH₂C(O)OR⁵⁴, —OCH₂C(O)NR⁵⁴R⁵⁵, —CH₂OR⁵⁴,        —CH₂NR⁵⁴R⁵⁵, and —C(O)OR⁵⁴; or    -   C₂₋₆-alkenyl and C₂₋₆-alkynyl, which may optionally be        substituted with one or more substituents selected from —CN,        —CF₃, —OCF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵ and C₁₋₆-alkyl, wherein        -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen,            C₁₋₆-alkyl, C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,            aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-, heteroaryl,            or aryl;        -   or        -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom,            together with the said nitrogen atom may form a 3 to 8            membered heterocyclic ring optionally containing one or two            further heteroatoms selected from nitrogen, oxygen and            sulfur, and optionally containing one or two double bonds.            Embodiment 117: A compound according to embodiment 138,            wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen, or        C₁₋₆-alkyl, C₁₋₆-alkyl-C₃₋₁₀-arylene-,        C₁₋₆-alkyl-C₃₋₁₀-heteroarylene-, C₃₋₁₀-aryl-C₁₋₆-alkylene-,        C₃₋₁₀-heteroaryl-C₁₋₆-alkylene-, C₃₋₁₀-heteroaryl, or        C₃₋₁₀-aryl.        Embodiment 118: A compound according to embodiment 141, wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment 119: A compound according to embodiment 142, wherein    -   R⁵⁴ is hydrogen.        Embodiment 120: A compound according to embodiment 142 or        embodiment 143, wherein    -   R⁵⁵ is hydrogen.        Embodiment 121: A compound according to embodiment 135, wherein        G¹ is        R⁵⁶, R⁵⁷, R⁵⁸, R⁵⁹, and R⁶⁰, independently of each other, are        hydrogen or halogen, —CN, —NO₂, C₁₋₆-alkyl, —CHF₂, —CF₃, —OCF₃,        —OCHF₂, —OCH₂CF₃, —OCF₂CHF₂, —S(O)₂CF₃, —SCF₃, —OR⁶¹, —NR⁶¹R⁶²,        —SR⁶¹, —NR⁶¹S(O)₂R⁶², —S(O)₂NR⁶¹R⁶², —S(O)NR⁶¹R⁶², —S(O)R⁶¹,        —S(O)₂R⁶¹, —C(O)NR⁶¹R⁶², —OC(O)NR⁶¹R⁶², —NR⁶¹C(O)R⁶²,        —CH₂C(O)NR⁶¹R⁶², —CH₂C(O)OR⁶¹, —OCH₂C(O)NR⁶¹R⁶², —CH₂OR⁶¹,        —CH₂NR⁶¹R⁶², —OC(O)R⁶¹, —C(O)R⁶¹ and —C(O)OR⁶¹; or        C₂₋₆-alkenyl and C₂₋₆-alkynyl, which may optionally be        substituted with one or more substituents selected from —CN,        —CF₃, —OCF₃, —OR⁶¹, —NR⁶¹R⁶² and C₁₋₆-alkyl; C₃₋₁₀-cycloalkyl,        C₄₋₈-cycloalkenyl, heterocyclyl,        C₃₋₁₀-cycloalkyl-C₁₋₆-alkylene-, C₃₋₁₀-cyclo-alkyl-C₁₋₆-alkoxy-,        C₃₋₁₀-cycloalkyloxy, C₃₋₁₀-cycloalkyl-C₁₋₆-alkylthio-,        C₃₋₁₀-cycloalkylthio, C₃₋₁₀-cycloalkyl-C₂₋₆-alkenylene-,        C₃₋₁₀-cycloalkyl-C₂₋₆-alkynylene-,        C₄₋₈-cycloalkenyl-C₁₋₆-alkylene-,        C₄₋₈-cycloalkenyl-C₂₋₆-alkenylene-,        C₄₋₈-cycloalkenyl-C₂₋₆-alkynylene-, heterocyclyl-C₁₋₆-alkylene-,        heterocyclyl-C₂₋₆-alkenylene-, heterocyclyl-C₂₋₆-alkynylene-; or        aryl, aryloxy, aryloxycarbonyl, aroyl, aryl-C₁₋₆-alkoxy-,        aryl-C₁₋₆-alkylene-, aryl-C₂₋₆-alkenylene-,        aryl-C₂₋₆-alkynylene-, heteroaryl, heteroaryl-C₁₋₆-alkylene-,        heteroaryl-C₂₋₆-alkenylene- and heteroaryl-C₂₋₆-alkynylene-, of        which the aryl and heteroaryl moieties optionally may be        substituted with one or more substituents selected from halogen,        —C(O)OR⁶¹, —CN, —CF₃, —OCF₃, —NO₂, —OR⁶¹, —NR⁶¹R⁶² or        C₁₋₆-alkyl; wherein    -   R⁶¹ and R⁶² independently of each other are hydrogen,        C₁₋₆-alkyl, C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,        aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-, heteroaryl, or        aryl;    -   or    -   R⁶¹ and R⁶², when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds.        Embodiment 122: A compound according to embodiment 146, wherein    -   R⁵⁶, R⁵⁷, R⁵⁸, R⁵⁹, and R⁶⁰ independently of each other are    -   halogen, —CN, —NO₂, C₁₋₆-alkyl, —CHF₂, —CF₃, —OR⁶¹, —NR⁶¹R⁶²,        —SR⁶¹, —NR⁶¹S(O)₂R⁶², —S(O)₂NR⁶¹R⁶², —S(O)NR⁶¹R⁶², —S(O)R⁶¹,        —S(O)₂R⁶¹, —C(O)NR⁶¹R⁶², —OC(O)NR⁶¹R⁶², —NR⁶¹C(O)R⁶²,        —CH₂C(O)NR⁶¹R⁶², —CH₂C(O)OR⁶¹, —OCH₂C(O)NR⁶¹R⁶², —CH₂OR⁶¹,        —CH₂NR⁶¹R⁶², and —C(O)OR⁶¹; or    -   C₂₋₆-alkenyl and C₂₋₆-alkynyl, which may optionally be        substituted with one or more substituents selected from —CN,        —CF₃, —OCF₃, —OR⁶¹, —NR⁶¹R⁶² and C₁₋₆-alkyl, wherein        -   R⁶¹ and R⁶² independently of each other are hydrogen,            C₁₋₆-alkyl, C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,            aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-, heteroaryl,            or aryl;        -   or        -   R⁶¹ and R⁶², when attached to the same nitrogen atom,            together with the said nitrogen atom may form a 3 to 8            membered heterocyclic ring optionally containing one or two            further heteroatoms selected from nitrogen, oxygen and            sulfur, and optionally containing one or two double bonds.            Embodiment 123: A compound according to embodiment 146 or            embodiment 147, wherein            R²⁴ or R²⁵ is —OR⁶¹.            Embodiment 124: A compound according to embodiment 147,            wherein    -   R⁶¹ and R⁶² independently of each other are hydrogen, or        C₁₋₆-alkyl, C₁₋₆-alkyl-C₃₋₁₀-arylene-,        C₁₋₆-alkyl-C₃₋₁₀-heteroarylene-, C₃₋₁₀-aryl-C₁₋₆-alkylene-,        C₃₋₁₀-heteroaryl-C₁₋₆-alkylene-, C₃₋₁₀-heteroaryl, or        C₃₋₁₀-aryl.        Embodiment 125: A compound according to embodiment 150, wherein    -   R⁶¹ and R⁶² independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment 126: A compound according to embodiment 151, wherein    -   R⁶¹ is hydrogen.        Embodiment 127: A compound according to embodiment 151 or        embodiment 152, wherein    -   R⁶² is hydrogen.        Embodiment 128: A compound according to any of embodiments 146        to 153, wherein    -   at least one of R⁵⁶, R⁵⁷, R⁵⁸, R⁵⁹, and R⁶⁰ are hydrogen.        Embodiment 129: A compound according to embodiment 154, wherein    -   at least two of R²³, R²⁴, R²⁵, and R²⁶ are hydrogen.        Embodiment 130: A compound according to embodiment 155, wherein    -   at least three of R²³, R²⁴, R²⁵, and R²⁶ are hydrogen.        Embodiment 131: A compound according to any of embodiments 1 to        156, wherein    -   L² is a direct bond, C₁₋₆-alkylene, C₂₋₆-alkenylene,        C₂₋₆-alkynylene, —N—R²⁰—, —C₁₋₆-alkylene-N(R²⁰)—,        —C₂₋₆-alkenylene-N(R²⁰)—, or —C₂₋₆-alkynylene-N(R²⁰)—, wherein        -   R²⁰ is as defined for embodiment 1.            Embodiment 132: A compound according to any of embodiments 1            to 153, wherein    -   L² is —N—R²⁰—, -alkylene-N(R²⁰)—, -alkenylene-N(R²⁰)—, or        -alkynylene-N(R²⁰)—, wherein        -   R²⁰ is as defined for embodiment 1.            Embodiment 133: A compound according to embodiment 157 or            embodiment 158, wherein    -   L² is —N—R²⁰—, —C₁₋₆-alkylene-N(R²⁰)—, —C₂₋₆-alkenylene-N(R²⁰)—,        or —C₂₋₆-alkynylene-N(R²⁰)—, wherein        -   R²⁰ is as defined for embodiment 1.            Embodiment 134: A compound according to embodiment 159,            wherein    -   L² is —N—R²⁰—, wherein        -   R²⁰ is as defined for embodiment 1.            Embodiment 135: A compound according to embodiment 157,            wherein    -   L² is a direct bond.        Embodiment 136: A compound according to any of embodiments 1 to        160, wherein    -   R²⁰ is hydrogen, or    -   R²⁰ is C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl,        C₃₋₁₀-cycloalkyl-W³—, C₃₋₁₀-heterocyclyl-W³—, C₃₋₁₀-aryl-W³—, or        C₄₋₁₀-heteroaryl-W³—, optionally substituted with one or more        substituents R³⁰, R³¹, and R³², wherein        -   W³, R³⁰, R³¹, and R³² are as defined for embodiment 1.            Embodiment 137: A compound according to embodiment 162,            wherein    -   W³ is alkylene.        Embodiment 138: A compound according to embodiment 163, wherein    -   W³ is C₂₋₆-alkylene.        Embodiment 139: A compound according to embodiment 162, wherein    -   W³ is a direct bond.        Embodiment 140: A compound according to any of embodiments 1 to        160, wherein    -   R²⁰ is hydrogen, alkyl, alkenyl, or alkynyl, optionally        substituted with one or more substituents R³⁰, R³¹, and R³²,        wherein        -   R³⁰, R³¹, and R³² are as defined for embodiment 1.            Embodiment 141: A compound according to any of embodiments            162 to 166, wherein    -   R²⁰ is hydrogen, or    -   R²⁰ is C₁₋₆-alkyl, C₁₋₆-alkenyl, or C₁₋₆-alkynyl, optionally        substituted with one or more substituents R³⁰, R³¹, and R³²,        wherein        -   R³⁰, R³¹, and R³² are as defined for embodiment 1.            Embodiment 142: A compound according to any of embodiments 1            to 167, wherein    -   R³⁰, R³¹, and R³² independently of each other are selected from        —CHF₂, —CF₃, —OCF₃, —OCHF₂, —OCH₂CF₃, —OCF₂CHF₂, —S(O)₂CF₃,        —SCF₃, —OR⁵², —NR⁵²R⁵³, —SR₅₂, —NR⁵⁴S(O)₂R⁵³, —S(O)₂NR⁵²R⁵³,        —S(O)NR⁵²R⁵³, —S(O)R⁵², —S(O)₂R⁵², —C(O)NR⁵²R⁵³, —OC(O)NR⁵²R⁵³,        —NR⁵²C(O)R⁵³, —CH₂C(O)NR⁵²R⁵³, —OCH₂C(O)NR⁵²R⁵³, —CH₂OR⁵²,        —CH₂NR⁵²R⁵³, —OC(O)R⁵², —C(O)R⁵² and —C(O)OR⁵², wherein        -   R⁵² and R⁵³ are as defined for embodiment 1.            Embodiment 143: A compound according to embodiment 168,            wherein    -   R⁵² and R⁵³, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds.        Embodiment 144: A compound according to any of embodiments 1 to        168, wherein    -   R⁵² and R⁵³ independently of each other are hydrogen,        C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene-heteroaryl-C₁₋₆-alkylene-heteroaryl, or aryl.        Embodiment 145: A compound according to embodiment 170, wherein    -   R⁵² and R⁵³ independently of each other are hydrogen,        C₁₋₆-alkyl, aryl-C₁₋₆-alkylene- or aryl.        Embodiment 146: A compound according to embodiment 171, wherein    -   R⁵² and R⁵³ independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment 147: A compound according to embodiment 172, wherein    -   R⁵² is hydrogen.        Embodiment 148: A compound according to embodiment 172 or        embodiment 173, wherein    -   R⁵³ is hydrogen.        Embodiment 149: A compound according to embodiment 167, wherein    -   R²⁰ is hydrogen.        Embodiment 150: A compound according to any of embodiments 1 to        175, wherein    -   L³ is —C(O)—.        Embodiment 151: A compound according to any of embodiments 1 to        176, wherein    -   R¹ is hydrogen, or    -   R¹ is C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl,        C₃₋₁₀-cycloalkyl-W⁴—, C₃₋₁₀-heterocyclyl-W⁴—, C₃₋₁₀-aryl-W⁴—, or        C₄₋₁₀-heteroaryl-W⁴—, optionally substituted with one or more        substituents R³³, R³⁴ and R³⁵ wherein        -   W⁴, R³³, R³⁴, and R³⁵ are as defined for embodiment 1.            Embodiment 152: A compound according to embodiment 180,            wherein    -   W⁴ is alkylene.        Embodiment 153: A compound according to embodiment 181, wherein    -   W⁴ is C₂₋₆-alkylene.        Embodiment 154: A compound according to embodiment 180, wherein    -   W⁴ is a direct bond.        Embodiment 155: A compound according to any of embodiments 1 to        176, wherein    -   R¹ is hydrogen, alkyl, alkenyl, or alkynyl, optionally        substituted with one or more substituents R³³, R³⁴, and R³⁵,        wherein        -   R³³, R³⁴, and R³⁵ are as defined for embodiment 1.            Embodiment 156: A compound according to any of embodiments            180 to 184, wherein    -   R¹ is hydrogen, C₁₋₆-alkyl, C₂₋₆-alkenyl, or C₂₋₆-alkynyl,        optionally substituted with one or more substituents R³³, R³⁴,        and R³⁵, wherein        -   R³³, R³⁴, and R³⁵ are as defined for embodiment 1.            Embodiment 157: A compound according to embodiment 185,            wherein    -   R¹ is hydrogen or C₁₋₆-alkyl optionally substituted with one or        more substituents R³³, R³⁴ and R³⁵ wherein        -   R³³, R³⁴, and R³⁵ are as defined for embodiment 1.            Embodiment 158: A compound according to any of embodiments 1            to 186, wherein    -   R³³, R³⁴, and R³⁵ independently of each other are selected from        —CHF₂, —CF₃, —OCF₃, —OCHF₂, —OCH₂CF₃, —OCF₂CHF₂, —S(O)₂CF₃,        —SCF₃, —OR⁵², —NR⁵²R⁵³, —SR₅₂, —NR⁵²S(O)₂R⁵³, —S(O)₂NR⁵²R⁵³,        —S(O)NR⁵²R⁵³, —S(O)R⁵², —S(O)₂R⁵², —C(O)NR⁵²R⁵³, —OC(O)NR⁵²R⁵³,        —NR⁵²C(O)R⁵³, —CH₂C(O)NR⁵²R⁵³, —OCH₂C(O)NR⁵²R⁵³, —CH₂OR⁵²,        —CH₂NR⁵²R⁵³, —OC(O)R⁵², —C(O)R⁵² and —C(O)OR⁵², wherein        -   R⁵² and R⁵³ are as defined for embodiment 1.            Embodiment 159: A compound according to embodiment 186,            wherein    -   R⁵² and R⁵³, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds.        Embodiment 160: A compound according to embodiment 186, wherein    -   R⁵² and R⁵³ independently of each other are hydrogen,        C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene-heteroaryl-C₁₋₆-alkylene-heteroaryl, or aryl.        Embodiment 161: A compound according to embodiment 189, wherein    -   R⁵² and R⁵³ independently of each other are hydrogen,        C₁₋₆-alkyl, aryl-C₁₋₆-alkylene- or aryl.        Embodiment 162: A compound according to embodiment 190, wherein    -   R⁵² and R⁵³ independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment 163: A compound according to embodiment 191, wherein    -   R⁵² is hydrogen.        Embodiment 164: A compound according to embodiment 191 or        embodiment 192, wherein    -   R⁵³ is hydrogen.        Embodiment 165: A compound according to embodiment 186, wherein    -   R¹ is hydrogen.        Embodiment 166: A compound according to any of embodiments 1 to        194, wherein    -   G² is heteroaryl, fused heterocyclylheteroaryl, or fused        cycloalkylheteroaryl, optionally substituted with one or more        substituents R⁴³, R⁴⁴, and R⁴⁵, wherein said heteroaryl group        possesses a nitrogen atom adjacent to the atom joining G² with        —N(R¹)—, and wherein        -   R⁴³, R⁴⁴, and R⁴⁵ are as defined for embodiment 1.            Embodiment 167: A compound according to embodiment 195,            wherein    -   G² is heteroaryl optionally substituted with one or more        substituents R⁴³, R⁴⁴, and R⁴⁵, wherein said heteroaryl group        possesses a nitrogen atom adjacent to the atom joining G² with        —N(R¹)—, and wherein        -   R⁴³, R⁴⁴, and R⁴⁵ are as defined for embodiment 1.            Embodiment 168: A compound according to embodiment 199,            wherein    -   G² is furanyl, thienyl, thiophenyl, pyrrolyl, imidazolyl,        pyrazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl,        isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridinyl,        pyridazinyl, pyrazinyl, pyrimidinyl, quinolinyl, isoquinolinyl,        benzofuranyl, benzothiophenyl, indolyl, or indazolyl, optionally        substituted with one or more substituents R⁴³, R⁴⁴, and R⁴⁵,        wherein        -   R⁴³, R⁴⁴, and R⁴⁵ are as defined for embodiment 1.            Embodiment 169: A compound according to any of embodiments 1            to 200, wherein    -   R⁴³, R⁴⁴, and R⁴⁵ independently of each other are selected from        halogen, —CN, —NO₂, C₁₋₆-alkyl, —CHF₂, —CF₃, —OCF₃, —OCHF₂,        —OCH₂CF₃, —OCF₂CHF₂, —S(O)₂CF₃, —SCF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵, —SR⁵⁴,        —NR⁵⁴S(O)₂R⁵⁵, —S(O)₂NR⁵⁴R⁵⁵, —S(O)NR⁵⁴R⁵⁵, —S(O)R⁵⁴, —S(O)₂R⁵⁴,        —C(O)NR⁵⁴R⁵⁵, —OC(O)NR⁵⁴R⁵⁵, —NR⁵⁴C(O)R⁵⁵, —CH₂C(O)NR⁵⁴R⁵⁵,        —CH₂C(O)OR⁵⁴, —OCH₂C(O)NR⁵⁴R⁵⁵, —CH₂OR⁵⁴, —CH₂NR⁵⁴R⁵⁵,        —OC(O)R⁵⁴, —C(O)R⁵⁴ and —C(O)OR⁵⁴, wherein    -   R⁵⁴ and R⁵⁵ are as defined for embodiment 1.        Embodiment 170: A compound according to embodiment 207, wherein    -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds, and optionally        substituted with one or more C₁₋₆-alkyl groups.        Embodiment 171: A compound according to embodiment 208, wherein    -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds.        Embodiment 172: A compound according to embodiment 207, wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen,        C₁₋₆-alkyl, aryl-C₁₋₆-alkylene- or aryl.        Embodiment 173: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen,        C₁₋₆-alkyl, C₃₋₁₀-aryl-C₁₋₆-alkylene- or C₃₋₁₀-aryl.        Embodiment 174: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment 175: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ is hydrogen.        Embodiment 176: A compound according to embodiment Error!        Reference source not found. or embodiment Error! Reference        source not found., wherein    -   R⁵⁵ is hydrogen.        Embodiment 177: A compound according to embodiment 207, wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen or        —(CHR⁶³)_(u)—(CHR⁶⁴)_(v)-Z, wherein        -   u is 1 or 2;        -   v is 0, 1 or 2;        -   R⁶³ and R⁶⁴ independently of each other are hydrogen,            C₁₋₆-alkyl, C₁₋₆-alkyl-C₃₋₁₀--arylene-C₃₋₁₀-aryl, hydroxy,            hydroxy-C₁₋₆-alkyl, amino, or amino-C₁₋₆-alkyl;        -   Z is hydrogen, —C—O—R⁶⁵, —C(O)O—R⁶⁵, —CONR⁶⁵R⁶⁶,            C₁₋₆-alkylamino, or di(C₁₋₆-alkyl)-amino, wherein            -   R⁶⁵ and R⁶⁶ independently of each other is hydrogen or                C₁₋₆-alkyl;        -   or        -   Z is a five or six membered ring wherein at least one ring            atom is nitrogen and the remaining ring atoms are either            carbon or oxygen.            Embodiment 178: A compound according to embodiment Error!            Reference source not found., wherein    -   u is 1; and    -   v is 0, or 1.        Embodiment 179: A compound according to embodiment Error!        Reference source not found. or embodiment Error! Reference        source not found., wherein    -   R⁶³ and R⁶⁴ independently of each other are hydrogen,        C₁₋₆-alkyl, hydroxy, hydroxy-C₁₋₆-alkyl, amino, or        amino-C₁₋₆-alkyl.        Embodiment 180: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   Z is —C—O—R⁶⁵, or —C(O)O—R⁶⁵, wherein        -   R⁶⁵ and R⁶⁶ independently of each other is hydrogen or            C₁₋₆-alkyl.            Embodiment 181: A compound according to any of embodiments            Error! Reference source not found. to Error! Reference            source not found., wherein    -   Z is a five or six membered ring where at least one ring atom is        nitrogen and the remaining ring atoms are either carbon or        oxygen.        Embodiment 182: A compound according to embodiment Error!        Reference source not found., wherein    -   Z is a five or six membered ring wherein at least one ring atom        is nitrogen, one ring atom is oxygen and the remaining ring        atoms are carbon.        Embodiment 183: A compound according to embodiment Error!        Reference source not found., wherein    -   Z is a five or six membered ring wherein at least one ring atom        is nitrogen, and the remaining ring atoms are carbon.        Embodiment 184: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   Z is a five or six membered ring wherein one ring atom is        nitrogen.        Embodiment 185: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   a nitrogen atom is the point of attachment of the Z group to the        —(CHR⁶³)—(CHR⁶⁴)_(v)— group.        Embodiment 186: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   R⁵⁵ is hydrogen.        Embodiment 187: A compound according to any of embodiments 195        to 207, wherein    -   G² is substituted with a substituent R⁴³, wherein        -   R⁴³ is halogen, —CN, —NO₂, C₁₋₆-alkyl, —CHF₂, —CF₃, —OCF₃,            —OCHF₂, —OCH₂CF₃, —OCF₂CHF₂, —S(O)₂CF₃, —SCF₃, —OR⁵⁴,            —NR⁵⁴R⁵⁵, —R⁵⁴, —NR⁵⁴S(O)₂R⁵⁵, —S(O)₂NR⁵⁴R⁵⁵, —S(O)NR⁵⁴R⁵⁵,            —S(O)R⁵⁴, —S(O)₂R⁵⁴, —C(O)NR⁵⁴R⁵⁵, —OC(O)NR⁵⁴R⁵⁵,            —NR⁵⁴C(O)R⁵⁵, —CH₂C(O)NR⁵⁴R⁵⁵, —CH₂C(O)OR⁵⁴,            —OCH₂C(O)NR⁵⁴R⁵⁵, —CH₂OR⁵⁴, —CH₂NR⁵⁴R⁵⁵, —OC(O)R⁵⁴, —C(O)R⁵⁴            or —C(O)OR⁵⁴, wherein            -   R⁵⁴ and R⁵⁵ are as defined for embodiment 1.                Embodiment 188: A compound according to embodiment                Error! Reference source not found., wherein    -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds, and optionally        substituted with one or more C₁₋₆-alkyl groups.        Embodiment 189: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds.        Embodiment 190: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen,        C₁₋₆-alkyl, aryl-C₁₋₆-alkylene- or aryl.        Embodiment 191: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen,        C₁₋₆-alkyl, C₃₋₁₀-aryl-C₁₋₆-alkylene- or C₃₋₁₀-aryl.        Embodiment 192: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment 193: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ is hydrogen.        Embodiment 194: A compound according to embodiment Error!        Reference source not found. or embodiment Error! Reference        source not found., wherein    -   R⁵⁵ is hydrogen.        Embodiment 195: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen or        —(CHR⁶³)—(CHR⁶⁴)_(v)-Z, wherein        -   u is 1 or 2;        -   v is 0, 1 or 2;        -   R⁶³ and R⁶⁴ independently of each other are hydrogen,            C₁₋₆-alkyl, C₁₋₆-alkyl-C₃₋₁₀-arylene-C₃₋₁₀-aryl, hydroxy,            hydroxy-C₁₋₆-alkyl, amino, or amino-C₁₋₆-alkyl;        -   Z is hydrogen, —C—O—R⁶⁵, —C(O)O—R⁶⁵, —CONR⁶⁵R⁶⁶,            C₁₋₆-alkylamino, or di(C₁₋₆-alkyl)-amino, wherein            -   R⁶⁵ and R⁶⁶ independently of each other is hydrogen or                C₁₋₆-alkyl;        -   or        -   Z is a five or six membered ring wherein at least one ring            atom is nitrogen and the remaining ring atoms are either            carbon or oxygen.            Embodiment 196: A compound according to embodiment Error!            Reference source not found., wherein    -   u is 1; and    -   v is 0, or 1.        Embodiment 197: A compound according to embodiment Error!        Reference source not found. or embodiment Error! Reference        source not found., wherein    -   R⁶³ and R⁶⁴ independently of each other are hydrogen,        C₁₋₆-alkyl, hydroxy, hydroxy-C₁₋₆-alkyl, amino, or        amino-C₁₋₆-alkyl.        Embodiment 198: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   Z is —C—O—R⁶⁵, or —C(O)O—R⁶⁵, wherein        -   R⁶⁵ and R⁶⁶ independently of each other is hydrogen or            C₁₋₆-alkyl.            Embodiment 199: A compound according to any of embodiments            Error! Reference source not found. to Error! Reference            source not found., wherein    -   Z is a five or six membered ring where at least one ring atom is        nitrogen and the remaining ring atoms are either carbon or        oxygen.        Embodiment 200: A compound according to embodiment Error!        Reference source not found., wherein    -   Z is a five or six membered ring wherein at least one ring atom        is nitrogen, one ring atom is oxygen and the remaining ring        atoms are carbon.        Embodiment 201: A compound according to embodiment Error!        Reference source not found., wherein    -   Z is a five or six membered ring wherein at least one ring atom        is nitrogen, and the remaining ring atoms are carbon.        Embodiment 202: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   Z is a five or six membered ring wherein one ring atom is        nitrogen.        Embodiment 203: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   a nitrogen atom is the point of attachment of the Z group to the        —(CHR⁶³)_(u)—(CHR⁶⁴)_(v)— group.        Embodiment 204: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   R⁵⁵ is hydrogen.        Embodiment 205: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁴³ is —CH₂C(O)OR⁵⁴, wherein        -   R⁵⁴ is as defined for embodiment 1.            Embodiment 206: A compound according to embodiment Error!            Reference source not found., wherein    -   R⁵⁴ is hydrogen, C₁₋₆-alkyl, aryl-C₁₋₆-alkylene- or aryl.        Embodiment 207: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ is hydrogen, C₁₋₆-alkyl, C₃₋₁₀-aryl-C₁₋₆-alkylene- or        C₃₋₁₀-aryl.        Embodiment 208: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ is hydrogen or C₁₋₆-alkyl.        Embodiment 209: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ is hydrogen.        Embodiment 210: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   R⁴³ is attached to the atom adjacent to the nitrogen atom        adjacent to the atom joining G² with —N(R¹)—.        Embodiment 211: A compound according to any of embodiments 195        to Error! Reference source not found., wherein        G² is    -   R⁴³, R⁴⁴, and R⁴⁵ independently of each other are hydrogen or as        defined for embodiment 1.        Embodiment 212: A compound according to embodiment Error!        Reference source not found., wherein        G² is    -   R⁴³, R⁴⁴, and R⁴⁵ independently of each other are hydrogen or as        defined for embodiment 1.        Embodiment 213: A compound according to embodiment Error!        Reference source not found. or embodiment Error! Reference        source not found., wherein    -   R⁴³, R⁴⁴, and R⁴⁵ independently of each other are selected from        hydrogen, halogen, —CN, —NO₂, C₁₋₆-alkyl, —CHF₂, —CF₃, —OCF₃,        —OCHF₂, —OCH₂CF₃, —OCF₂CHF₂, —S(O)₂CF₃, —SCF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵,        —SR⁵⁴, —NR⁵⁴S(O)₂R⁵⁵, —S(O)₂NR⁵⁴R⁵⁵, —S(O)NR⁵⁴R⁵⁵, —S(O)R⁵⁴,        —S(O)₂R⁵⁴, —C(O)NR⁵⁴R⁵⁵, —OC(O)NR⁵⁴R⁵⁵, —NR⁵⁴C(O)R⁵⁵,        —CH₂C(O)NR⁵⁴R⁵⁵, —CH₂C(O)OR⁵⁴, —OCH₂C(O)NR⁵⁴R⁵⁵, —CH₂OR⁵⁴,        —CH₂NR⁵⁴R⁵⁵, —OC(O)R⁵⁴, —C(O)R⁵⁴ and —C(O)OR⁵⁴, wherein        -   R⁵⁴ and R⁵⁵ are as defined for embodiment 1.            Embodiment 214: A compound according to embodiment Error!            Reference source not found., wherein    -   R⁴³ is halogen, —CN, —NO₂, C₁₋₆-alkyl, —CHF₂, —CF₃, —OCF₃,        —OCHF₂, —OCH₂CF₃, —OCF₂CHF₂, —S(O)₂CF₃, —SCF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵,        —SR⁵⁴, —NR⁵⁴S(O)₂R⁵⁵, —S(O)₂NR⁵⁴R⁵⁵, —S(O)NR⁵⁴R⁵⁵, —S(O)R⁵⁴,        —S(O)₂R⁵⁴, —C(O)NR⁵⁴R⁵⁵, —OC(O)NR⁵⁴R⁵⁵, —NR⁵⁴C(O)R⁵⁵,        —CH₂C(O)NR⁵⁴R⁵⁵, —CH₂C(O)OR⁵⁴, —OCH₂C(O)NR⁵⁴R⁵⁵, —CH₂OR⁵⁴,        —CH₂NR⁵⁴R⁵⁵, —OC(O)R⁵⁴, —C(O)R⁵⁴ or —C(O)OR⁵⁴, wherein        -   R⁵⁴ and R⁵⁵ are as defined for embodiment 1.            Embodiment 215: A compound according to embodiment Error!            Reference source not found. or Error! Reference source not            found., wherein    -   R⁴³ is —C(O)OR⁵⁴, —CH₂C(O)OR⁵⁴, —C(O)NR⁵⁴R⁵⁵, or        —CH₂C(O)NR⁵⁴R⁵⁵, wherein        -   R⁵⁴ and R⁵⁵ are as defined for embodiment 1.            Embodiment 216: A compound according to embodiment Error!            Reference source not found. or Error! Reference source not            found., wherein    -   R⁴⁴ is alkyl or hydrogen.        Embodiment 217: A compound according to embodiment Error!        Reference source not found., wherein R⁴⁴ is C₁₋₆-alkyl or        hydrogen.        Embodiment 218: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁴⁴ is hydrogen.        Embodiment 219: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁴⁴ is halogen, —CN, —NO₂, C₁₋₆-alkyl, —CHF₂, —CF₃, —OCF₃,        —OCHF₂, —OCH₂CF₃, —OCF₂CHF₂, —S(O)₂CF₃, —SCF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵,        —SR⁵⁴, —NR⁵⁴S(O)₂R⁵⁵, —S(O)₂NR⁵⁴R⁵⁵, —S(O)NR⁵⁴R⁵⁵, —S(O)R⁵⁴,        —S(O)₂R⁵⁴, —C(O)NR⁵⁴R⁵⁵, —OC(O)NR⁵⁴R⁵⁵, —NR⁵⁴C(O)R⁵⁵,        —CH₂C(O)NR⁵⁴R⁵⁵, —CH₂C(O)OR⁵⁴, —OCH₂C(O)NR⁵⁴R⁵⁵, —CH₂OR⁵⁴,        —CH₂NR⁵⁴R⁵⁵, —OC(O)R⁵⁴, —C(O)R⁵⁴ or —C(O)OR⁵⁴, wherein        -   R⁵⁴ and R⁵⁵ are as defined for embodiment 1.            Embodiment 220: A compound according to embodiment Error!            Reference source not found. or embodiment Error! Reference            source not found., wherein    -   R⁴⁴ is —C(O)OR⁵⁴, —CH₂C(O)OR⁵⁴, —C(O)NR⁵⁴R⁵⁵, or        —CH₂C(O)NR⁵⁴R⁵⁵, wherein        -   R⁵⁴ and R⁵⁵ are as defined for embodiment 1.            Embodiment 221: A compound according to embodiment Error!            Reference source not found. or Error! Reference source not            found., wherein    -   R⁴³ is alkyl or hydrogen.        Embodiment 222: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁴³ is C: 6-alkyl or hydrogen.        Embodiment 223: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁴³ is hydrogen.        Embodiment 224: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   R⁴⁵ is hydrogen.        Embodiment 225: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds, and optionally        substituted with one or more C₁₋₆-alkyl groups.        Embodiment 226: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds.        Embodiment 227: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen,        C₁₋₆-alkyl, aryl-C₁₋₆-alkylene- or aryl.        Embodiment 228: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen,        C₁₋₆-alkyl, aryl-C₁₋₆-alkylene- or aryl.        Embodiment 229: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment 230: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁵⁴ is hydrogen.        Embodiment 231: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   R⁵⁵ is hydrogen.        Embodiment 232: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen or        —(CHR⁶³)_(u)—(CHR⁶⁴)_(v)-Z, wherein        -   u is 1 or 2;        -   v is 0, 1 or 2;        -   R⁶³ and R⁶⁴ independently of each other are hydrogen,            C₁₋₆-alkyl, C₁₋₆-alkyl-C₃₋₁₀-arylene-C₃₋₁₀-aryl, hydroxy,            hydroxy-C₁₋₆-alkyl, amino, or amino-C₁₋₆-alkyl;        -   Z is hydrogen, —C—O—R⁶⁵, —C(O)O—R⁶⁵, —CONR⁶⁵R⁶⁶,            C₁₋₆-alkylamino, or di(C₁₋₆-alkyl)-amino, wherein            -   R⁶⁵ and R⁶⁶ independently of each other is hydrogen or                C₁₋₆-alkyl;        -   or        -   Z is a five or six membered ring wherein at least one ring            atom is nitrogen and the remaining ring atoms are either            carbon or oxygen.            Embodiment 233: A compound according to embodiment Error!            Reference source not found., wherein    -   u is 1; and    -   v is 0, or 1.        Embodiment 234: A compound according to embodiment Error!        Reference source not found. or embodiment Error! Reference        source not found., wherein    -   R⁶³ and R⁶⁴ independently of each other are hydrogen,        C₁₋₆-alkyl, hydroxy, hydroxy-C₁₋₆-alkyl, amino, or        amino-C₁₋₆-alkyl.        Embodiment 235: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   Z is —C—O—R⁶⁵, or —C(O)O—R⁶⁵, wherein        -   R⁶⁵ and R⁶⁶ independently of each other is hydrogen or            C₁₋₆-alkyl.            Embodiment 236: A compound according to any of embodiments            Error! Reference source not found. to Error! Reference            source not found., wherein    -   Z is a five or six membered ring where at least one ring atom is        nitrogen and the remaining ring atoms are either carbon or        oxygen.        Embodiment 237: A compound according to embodiment Error!        Reference source not found., wherein    -   Z is a five or six membered ring wherein at least one ring atom        is nitrogen, one ring atom is oxygen and the remaining ring        atoms are carbon.        Embodiment 238: A compound according to embodiment Error!        Reference source not found., wherein    -   Z is a five or six membered ring wherein at least one ring atom        is nitrogen, and the remaining ring atoms are carbon.        Embodiment 239: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   Z is a five or six membered ring wherein one ring atom is        nitrogen.        Embodiment 240: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   a nitrogen atom is the point of attachment of the Z group to the        —(CHR⁶³)_(u)—(CHR⁶⁴)_(v)— group.        Embodiment 241: A compound according to any of embodiments        Error! Reference source not found. to Error! Reference source        not found., wherein    -   R⁵⁵ is hydrogen.        Embodiment 242: A compound according to embodiment Error!        Reference source not found., wherein    -   R⁴⁴ is hydrogen.        Embodiment 243: A compound according to embodiment Error!        Reference source not found. or embodiment Error! Reference        source not found., wherein    -   R⁴³ is hydrogen.        Embodiment 244: A compound according to embodiment Error!        Reference source not found. or embodiment Error! Reference        source not found., wherein    -   R⁴⁵ is hydrogen.        Embodiment 245: A compound according to embodiment 1, which is,

-   N-(2-phenoxyphenyl)-N′-(thiazol-2-yl)urea,

-   N-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]-N′-(thizol-2-yl)sulfamide,

-   1-(2-phenoxyphenyl)-5-(thiazol-2-yl)biuret,

-   2-[([[(2-phenoxyanilino)sulfonyl]amino]carbonyl)amino]thiazole,

-   N-(2-phenylsulfanylphenyl)-N′-(thiazol-2-yl)urea,

-   N-(2-phenylsulfonylphenyl)-N′-(thiazol-2-yl)urea,

-   N-(2-benzylphenyl)-N′-(thiazol-2-yl)urea,

-   N-(2-benzoylphenyl)-N′-(thiazol-2-yl)urea,

-   N-[2-(phenylamino)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-fluoro-6-(4-methoxyphenoxy)benzyl]-N′-(thiazol-2-yl)urea,

-   N-(2-benzyloxyphenyl)-N′-(thiazol-2-yl)urea,

-   N-[2-(2,3,4-trimethoxybenzyloxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-(2-ethoxyphenyl)-N′-(thiazol-2-yl)urea,

-   N-(2-phenoxyphenyl)-N′-(pyridin-2-yl)urea,

-   N-(2-phenoxyphenyl)-N′-[(4-methoxycarbonylmethyl)thiazol-2-yl]urea,

-   N-methyl-N-(2-phenoxyphenyl)-N′-(thiazol-2-yl)urea,

-   N-isopropyl-N-(2-phenoxyphenyl)-N′-(thiazol-2-yl)urea,

-   N-[2-(4-methoxyphenoxy)phenyl)-N′-(thiazol-2-yl)urea,

-   N-[2-(4-fluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(4-chlorophenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(4-cyanophenoxy)phenyl]-N′-thiazolylurea,

-   N-[2-(4-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(4-isopropylphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(3,4-difluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(3,4-dichlorophenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(4-chloro-3-methylphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(3,4-dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(3,4-methylenedioxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,4-dichlorophenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,4-difluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(4-fluoro-2-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(4-methoxy-2-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(3-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(3-fluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(3-trifluoromethylphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-methylphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-isopropoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-fluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-methylsulfanylphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-methylsulfonylphenoxy)phenyl]-N′-thiazolylurea,

-   N-[2-(2-trifluoromethylphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,6-dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,6-difluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-fluoro-6-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-methoxy-6-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[(3-methoxy-2-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,3-dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,3,4-trichlorophenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,4,6-trifluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,4-dichloronaphth-1-oxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-methoxyphenoxy)-5-(methylsulfonyl)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[5-cyano-2-(2-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[5-fluoro-2-(2-methylsulfanylphenoxy)phenyl]-N′-thiazolylurea,

-   N-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]-N′(thiazol-2-yl)urea,

-   N-[2-(3,4-difluorophenoxy)-5-fluorophenyl]-N′-(thiazol-2-yl)urea,

-   N-[5-fluoro-2-(4-fluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,4-dichlorophenoxy)-5-fluorophenyl]-N′-(thiazol-2-yl)urea,

-   N-[5-fluoro-2-(4-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[5-fluoro-2-(2-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[5-fluoro-2-(2-trifluoromethylphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[5-fluoro-2-(naphth-2-oxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,3-dimethoxyphenoxy)-6-fluorophenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(4-fluoro-2-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,3-dimethoxyphenoxy)-4-fluorophenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-fluoro-6-methoxyphenoxy)-4-methoxyphenyl]-N′-(thiazol-2-yl)urea,

-   N-[3-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,3-dimethoxyphenoxy)-5-methoxyphenyl]-N′-thiazol-2-yl)urea,

-   N-[2-(2,3-dimethoxyphenoxy)-4-methylphenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,3-dimethoxyphenoxy)-3-methylphenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-chlorophenoxy)-5-chlorophenyl]-N′-(thiazol-2-yl)urea,

-   N-[5-chloro-2-(4-chloro-3-methylphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[4,5-difluoro-2-(2,3-dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[4,5-dichloro-2-(2,3-dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[5-chloro-2-(2,3-dimethoxyphenoxy)-4-dimethylaminophenyl]-N′-(thiazol-2-yl)urea,

-   N-[5-chloro-2-(2,3-dimethoxyphenoxy)-4-(4-morpholino)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,4-difluorophenoxy)pyridin-3-yl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-fluorophenoxy)pyridin-3-yl]-N′-[thiazol-2-yl]urea,

-   N-[2-(2-methoxyphenoxy)pyridin-3-yl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,3-dimethoxyphenoxy)pyridin-3-yl]-N-(thiazol-2-yl)urea,

-   N-[4-chloro-2-(2-chlorobenzoyl)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[4-chloro-2-(2-fluorobenzoyl)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,4-difluorophenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea,

-   1-[2-(2-fluorophenylsulfanyl)phenyl]-3-(thiazol-2-yl)urea,

-   N-[2-(2-chloro-4-fluorophenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2,3-dichlorophenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(3,5-dimethylphenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-methoxycarbonylphenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-methoxyphenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-pyridinylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea,

-   N-(2-propyloxyphenyl)-N′-(thiazol-2-yl)urea,

-   N-(2-butyloxyphenyl)-N′-(thiazol-2-yl)urea,

-   N-(2-(cyclopentyloxyphenyl)-N′-(thiazol-2-yl)urea,

-   N-(2-isopropoxyphenyl)-N′-(thiazol-2-yl)urea,

-   N-[2-(2-methylpropoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(cyclopentylmethoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(3-pentoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-pentoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   N-[2-(2-methoxyethoxy)phenyl]-N′-(thiazol-2-yl)urea,

-   (2-[3-(2-benzylphenyl)ureido]thiazol-4-yl)acetic acid,

-   (2-[3-(2-benzoyl-4-chlorophenyl)ureido]thiazol-4-yl)acetic acid,

-   (2-[3-(2-(2-methylphenoxy)phenyl)ureido]thiazol-4-yl)acetic acid,

-   (2-[3-(2-(4-methoxyphenoxy)-5-(trifluoromethyl)phenyl)ureido]thiazol-4-yl)acetic    acid,

-   {2-[3-(2-phenoxyphenyl)ureido]thiazol-4-yl}acetic acid,

-   2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazole-4-carboxylic    acid,

-   2-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazole-4-carboxylic    acid ethyl ester,

-   (2-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazol-4-yl)acetic    acid ethyl ester,

-   (2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)acetic    acid,

-   2-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazole-4-carboxylic    acid,

-   (2-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazol-4-yl)acetic    acid,

-   2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}-4-methylthiazole-5-carboxylic    acid ethyl ester,

-   2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}-4-methylthiazole-5-carboxylic    acid,

-   N-ethyl-2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)acetamide,

-   2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)-N-(2-methoxy-ethyl)acetamide,

-   2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)-N-(2-morpholin-4-ylethyl)acetamide,

-   [2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)acetylamino]acetic    acid methyl ester,

-   2-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazole-4-carboxylic    acid (2-methoxyethyl)amide,

-   [2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)acetylamino]acetic    acid,

-   2-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazole-4-carboxylic    acid ethylamide,

-   [(2-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazole-4-carbonyl)amino]acetic    acid methyl ester,

-   (5-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}-[1,3,4]thiadiazol-2-yl)acetic    acid ethyl ester,

-   [(2-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazole-4-carbonyl)amino]acetic    acid,

-   (5-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}-[1,3,4]thiadiazol-2-yl)acetic    acid,

-   5-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}-[1,3,4]thiadiazole-2-carboxylic    acid ethyl ester,

-   (5-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}-[1,3,4]thiadiazol-2-yl)acetic    acid ethyl ester,

-   3-[2-(2-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazol-4-yl)acetylamino]propionic    acid methyl ester,

-   2-(2-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazol-4-yl)-N-(2-morpholin-4-ylethyl)acetamide,

-   [(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazole-4-carbonyl)amino]acetic    acid methyl ester,

-   3-[2-(2-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazol-4-yl)acetylamino]propionic    acid,

-   [(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazole-4-carbonyl)amino]acetic    acid,

-   (R)    3-[(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazole-4-carbonyl)amino]-2-hydroxy-propionic    acid,

-   2-[(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazole-4-carbonyl)amino]-3-hydroxy-propionic    acid,

-   1-(2-cyclopentanecarbonyl-4-methylphenyl)-3-thiazol-2-yl-urea,

-   1-(2-isobutyryl-4-methylphenyl)-3-thiazol-2-yl-urea,

-   1-[5-fluoro-2-(3-methylbutyryl)phenyl]-3-thiazol-2-yl-urea,

-   1-[5-methyl-2-(3-methylbutyryl)phenyl]-3-thiazol-2-yl-urea,

-   [3-cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)phenyl]acetic acid    ethyl ester,

-   [3-cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)phenyl]acetic acid,

-   2-[3-cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)phenyl]-N-methylacetamide,

-   {2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid ethyl ester,

-   {2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}acetic    acid,

-   {3-cyclopentanecarbonyl-4-{3-(4-ethoxycarbonylmethylthiazol-2-yl)-ureido}phenyl}acetic    acid ethyl ester,

-   1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea,

-   2-[3-(2-cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazole-4-carboxylic    acid ethyl ester,

-   2-[3-(2-cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazole-4-carboxylic    acid,

-   2-[3-(2-cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazole-4-carboxamide,

-   2-{2-[3-(2-cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazole-4-yl}-acetamide,

-   2-{2-[3-(2-cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazol-4-yl}-N-methyl-acetamide

-   4-(2-{2-[3-(2-cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazol-4-yl}-acetyl)-1-methyl-piperazinium    chloride,

-   1-[4-methyl-2-(2-methylpropoxy)phenyl]-3-thiazol-2-yl-urea,

-   {2-[3-(4-methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-acetic    acid, or

-   {2-[3-(4-methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-N-methyl-acetamide.    Embodiment 246: A compound according to any of embodiments 1 to    Error! Reference source not found., which compound is an activator    of glucokinase, when tested in the Glucokinase Activation Assay (I)    disclosed herein at a glucose concentration of 2 mM.    Embodiment 247: A compound according to any of embodiments 1 to 281,    which compound is an activator of glucokinase, when tested in the    Glucokinase Activation Assay (I) disclosed herein at a glucose    concentration of from 10 to 15 mM.    Embodiment 248: A compound according to any of embodiments 1 to 282,    which compound, at a concentration of 30 μM, is capable of providing    an at least 1.5, such as at least 1.7, for instance at least 2.0    fold activation of glucokinase in the Glucokinase Activation    Assay (I) disclosed herein at a glucose concentration of 2 mM.    Embodiment 249: A compound according to any of embodiments 1 to 283,    which compound, at a concentration of 30 μM, is capable of providing    an at least 1.5, such as at least 1.7, for instance at least 2.0    fold activation of glucokinase in the Glucokinase Activation    Assay (I) disclosed herein at a glucose concentration of from 10 to    15 mM.    Embodiment 250: A compound according to any of embodiments 1 to 284,    which at a concentration of 5 μM is capable of providing an at least    1.5, such as at least 1.7, for instance at least 2.0 fold activation    of glucokinase in the Glucokinase Activation Assay (I) disclosed    herein at a glucose concentration of 2 mM.    Embodiment 251: A compound according to any of embodiments 1 to 285,    which at a concentration of 5 μM is capable of providing an at least    1.5, such as at least 1.7, for instance at least 2.0 fold activation    of glucokinase in the Glucokinase Activation Assay (I) disclosed    herein at a glucose concentration of from 10 to 15 mM.    Embodiment 252: A glucose kinase activator compound defined as a    compound which at a compound concentration of at or below 30 μM at a    glucose concentration of 2 mM in the Glucokinase. Activation    Assay (I) disclosed herein gives 1.5-fold higher glucokinase    activity than measured at a glucose concentration of 2 mM in the    Glucokinase Activation Assay (I) without compound, where the    increase in glucokinase activity provided by the compound increases    with decreasing concentrations of glucose.    Embodiment 253: A compound according to any of embodiments 1 to 286,    which compound provides an increase in glucokinase activity, where    the increase in glucokinase activity provided by the compound    increases with decreasing concentrations of glucose.    Embodiment 254: A compound according to embodiment 287 or embodiment    288, which provides an increase in glucokinase activity in    Glucokinase Activation Assay (I) disclosed herein at a glucose    concentration of 5 mM, which increase is significantly higher than    the increase in glucokinase activity provided by the compound in    Glucokinase Activation Assay (I) disclosed herein at a glucose    concentration of 15 mM.    Embodiment 255: A compound according to any of embodiments 287 to    289, which at a compound concentration of 10 μM provides an increase    in glucokinase activity in Glucokinase Activation Assay (I)    disclosed herein at a glucose concentration of 5 mM, which increase    is significantly higher than the increase in glucokinase activity    provided by the compound at a compound concentration of 10 μM in    Glucokinase Activation Assay (I) disclosed herein at a glucose    concentration of 15 mM.    Embodiment 256: A compound according to any of embodiments 287 to    290, which at a compound concentration of 10 μM provides an increase    in glucokinase activity in Glucokinase Activation Assay (I)    disclosed herein at a glucose concentration of 5 mM, which increase    is at least 1.1 fold higher, such as at least 1.2 fold higher, for    instance at least 1.3 fold higher, such as at least 1.4 fold higher,    for instance 1.5 fold higher, such as at least 1.6 fold higher, for    instance at least 1.7 fold higher, such as at least 1.8 fold higher,    for instance at least 1.9 fold higher, such as at least 2.0 fold    higher than the increase in glucokinase activity provided by the    compound at a compound concentration of 10 μM in Glucokinase    Activation Assay (I) disclosed herein at a glucose concentration of    15 mM.    Embodiment 257: A glucose kinase activator compound defined as a    compound which at a compound concentration of at or below 30 μM at a    glucose concentration of 2 mM in the Glucokinase Activation    Assay (I) disclosed herein gives 1.5-fold higher glucokinase    activity than measured at a glucose concentration of 2 mM in the    Glucokinase Activation Assay (I) without compound, which glucose    kinase activator compound increases glucose utilization in the liver    without inducing any increase in insulin secretion in response to    glucose.    Embodiment 258: A glucose kinase activator compound defined as a    compound which at a compound concentration of at or below 30 μM at a    glucose concentration of 2 mM in the Glucokinase Activation    Assay (I) disclosed herein gives 1.5-fold higher glucokinase    activity than measured at a glucose concentration of 2 mM in the    Glucokinase Activation Assay (I) without compound, which glucokinase    activator compound shows a significantly higher activity in isolated    hepatocytes compared to the activity of the glucokinase compound in    Ins-1 cells.    Embodiment 259: A compound according to any of embodiments 1 to 291,    which compound increases glucose utilization in the liver without    inducing any increase in insulin secretion in response to glucose.    Embodiment 260: A compound according to any of embodiments 1 to 291,    which compound shows a significantly higher activity in isolated    hepatocytes compared to the activity of the compound in Ins-1 cells.    Embodiment 261: A compound according to any of embodiments 292 to    295, which compound shows a significantly higher activity in    isolated hepatocytes measured as described in the Glucokinase    Activity Assay (II) compared to the activity of the compound in    Ins-1 cells measured as described in the Glucokinase Activity Assay    (III).    Embodiment 262: A compound according to embodiment 296, which    compound shows an activity in isolated hepatocytes measured as    described in the Glucokinase Activity Assay (II) which activity is    at least 1.1 fold higher, such as at least 1.2 fold higher, for    instance at least 1.3 fold higher, such as at least 1.4 fold higher,    for instance 1.5 fold higher, such as at least 1.6 fold higher, for    instance at least 1.7 fold higher, such as at least 1.8 fold higher,    for instance at least 1.9 fold higher, such as at least 2.0 fold    higher, for instance at least a 3.0 fold higher, such as at least a    4.0 fold higher, for instance at least 5.0 fold higher, such as at    least 10 fold higher than the activity of the compound in Ins-1    cells measured as described in the Glucokinase Activity Assay (III).    Embodiment 263: A compound according to embodiment 296, which    compound shows no activity in the Ins-1 cells measured as described    in the Glucokinase Activity Assay (III).    Embodiment 264: A compound according to any one of embodiments 1 to    298, which is an agent useful for the treatment of an indication    selected from the group consisting of hyperglycemia, IGT, insulin    resistance syndrome, syndrome X, type 2 diabetes, type 1 diabetes,    dyslipidemia, hypertension, and obesity.    Embodiment 265: A compound according to any one of embodiments 1 to    301 for use as a medicament.    Embodiment 266: A compound according to any one of embodiments 1 to    301 for treatment of hyperglycemia, for treatment of IGT, for    treatment of Syndrome X, for treatment of type 2 diabetes, for    treatment of type 1 diabetes, for treatment of dyslipidemia, for    treatment of hyperlipidemia, for treatment of hypertension, for    treatment of obesity, for lowering of food intake, for appetite    regulation, for regulating feeding behaviour, or for enhancing the    secretion of enteroincretins, such as GLP-1. In a further aspect the    invention provides in an Embodiment A1 a compound of the general    formula (I)    A¹ is selected from the group consisting of arylene, heteroarylene,    fused cycloalkylarylene, fused heterocyclylarylene, fused    cycloalkylheteroarylene, or fused heterocyclylheteroarylene;    optionally substituted with one or more substitutents R²³, R²⁴, R²⁵,    R²⁶, and R²⁷, wherein    -   R²³, R²⁴, R²⁵, R²⁶, and R²⁷ independently of each other are        selected from the group consisting of    -   halogen, —C(O)OR², —C(O)R², —CN, —CF₃, —OCF₃, —NO₂, —OR²,        —NR²R³, C₁₋₆-alkyl-Z-, C₂₋₆-alkenyl-Z-, C₂₋₆-alkynyl-Z-,        aryl-C₁₋₆-alkylene-Z-, heteroaryl-C₁₋₆-alkylene-Z-,        heterocyclyl-C₁₋₆-alkylene-Z-, cycloalkyl-C₁₋₆-alkylene-Z-,        N(R⁴R⁵)—C₁₋₆-alkylene-Z-, R⁶—W¹-Z-, R⁶—W¹—C₁₋₆-alkylene-Z-,        R⁶—W¹—C₁₋₆-arylene-Z-, R⁶—W¹-heteroarylene-Z-,        R⁶—W¹-heterocyclylene-Z-, R⁶—W¹—N(R⁴)-Z-, R⁶—N(R⁴)-Z,        R⁶—W¹—C₁₋₆-alkylene-Z-, heterocyclyl-Z-C₁₋₆-alkylene-,        heterocyclyl-C₁₋₆-alkylene-Z-C₁₋₆-alkylene-,        C₃₋₁₀-cycloalkyl-Z-C₁₋₆-alkylene-,        C₃₋₁₀-cycloalkyl-C₁₋₆-alkylene-Z-C₁₋₆-alkylene-,        C₃₋₁₀-cycloalkyl-arylene-Z-, heterocyclyl-arylene-Z-,        C₃₋₁₀-cycloalkyl-heteroarylene-Z-,        heterocyclyl-heteroarylene-Z-, aryl-C₃₋₁₀-cycloalkylene-Z-,        aryl-heterocyclylene-Z-, heteroaryl-C₃₋₁₀-cycloalkylene-Z-,        heteroaryl-heterocyclylene-Z-,        heterocyclyl-C₃₋₁₀-cycloalkylene-Z-, aryl-heteroarylene-Z-,        heteroaryl-arylene-Z-, aryl-arylene-Z-,        heteroaryl-heteroarylene-Z-, wherein any mono- or divalent        C₁₋₆-alkyl, C₃₋₁₀-cycloalkyl, heterocyclyl, aryl or heteroaryl        moiety can optionally be substituted with one or more        substituents independently selected from R², and wherein        -   R² and R³ independently of each other are hydrogen, halogen,            hydroxy, —CN, —CF₃, —OCF₃, —NO₂, —C(O)OH, —NH₂, C₁₋₆-alkyl,            C₁₋₆-alkoxy, aryloxy, R⁶-Z-, aryl-C₁₋₆-alkylene-,            heteroaryl-C₁₋₆-alkylene-, C₁₋₆-alkyl-arylene-,            C₁₋₆-alkyl-heteroarylene-, heteroaryl, or aryl;        -   or        -   R² and R³, when attached to the same nitrogen atom, together            with said nitrogen atom may form a 3 to 8 membered            heterocyclic ring optionally containing one or two further            heteroatoms selected from nitrogen, oxygen and sulfur, and            optionally containing one or two double bonds;    -   Z and W¹ independently of each other are a direct bond, —O—,        —N(R⁷)—, —N(R⁷)C(R⁷R⁸)—, —S—, —SO₂—, —C(O)N(R⁷)—, —N(R⁷)C(O)—,        —N(R⁷)C(O)C(R⁷R⁸)—, —N(R⁷)CON(R⁸)—, —N(R⁷)SO₂—, —SO₂N(R⁷)—,        —C(O)—, —C(O)—O—, —N(R⁷)SO₂N(R⁸)—, or —O—C(O)—, wherein        -   R⁷ and R⁸ in each individual case independently of each            other are hydrogen or C₁₋₆-alkyl; and    -   R⁴, R⁵, and R⁶ independently of each other are selected from the        group consisting of hydrogen, cyano, halogen, aryl, heteroaryl,        heteroaryl-C₁₋₆-alkylene-, aryl-C₁₋₆-alkylene-,        C₃₋₁₀-cycloalkyl, heterocyclyl optionally substituted with one        or more C₁₋₆-alkyl, or C₁₋₆-alkyl optionally substituted with        halogen, —S(O)₂CH₃ or COOH;    -   or    -   R⁴ and R⁵ may be taken together to form a ring having the        formula —(CH₂)_(j)-Q-(CH₂)_(k)— bonded to the nitrogen atom to        which R⁴ and R⁵ are attached, wherein        -   j and k independently of each other is 1, 2, 3, or 4; and        -   Q is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—,            —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —NHSO₂—, —SO₂NH—, —C(O)—O—,            —O—C(O)—, —NHSO₂NH—,        -   wherein            -   R⁹ and R¹⁰ independently of each other are selected from                the group consisting of hydrogen, aryl, C₁₋₆-alkyl, and                aryl-alkylene-;    -   L¹ is a bond, -D-C₁₋₆-alkylene-E-, -D-C₂₋₆-alkenylene-E-,        -D-C₂₋₆-alkynylene-E-, -D-cycloalkylene-E-,        -D-heterocyclylene-E-, —O—, —S—, —S(O)—, —S(O)₂—, —C(O)—,        —N(R¹¹)—, or —C(═N—OR¹²)—, wherein    -   D and E independently of each other are a direct bond, —O— or        —S—;    -   R¹¹ is selected from hydrogen, C₁₋₆-alkyl, aryl, carbamoyl,        aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-,        C₁₋₆-alkyl-O—C(O)—, aryl-C₁₋₆-alkylene-O—C(O)—,        heteroaryl-C₁₋₆-alkylene-O—C(O)—, C₁₋₆-alkyl-NH—C(O)—,        aryl-C₁₋₆-alkylene-NH—C(O)—, heteroaryl-C₁₋₆-alkylene-NH—C(O)—,        C₁₋₆-alkyl-SO₂—, aryl-C₁₋₆-alkylene-SO₂—,        heteroaryl-C₁₋₆-alkylene-SO₂—, aryl-SO₂—, heteroaryl-SO₂—,        C₁₋₆-alkyl-NH—SO₂—, aryl-C₁₋₆-alkylene-NH—SO₂—,        heteroaryl-C₁₋₆-alkylene-NH—SO₂—, C₁₋₆-alkyl-C(O)—,        aryl-C₁₋₆-alkylene-C(O)—, heteroaryl-C₁₋₆-alkylene-C(O)—,        C₁₋₆-alkyl-Y—, aryl-Y—, heteroaryl-Y—, aryl-C₁₋₆-alkylene-Y—,        heteroaryl-C₁₋₆-alkylene-Y—, N(R¹³)(R¹⁴)—C₁₋₆-alkylene-Y—, and        R¹⁵—W²—C₁₋₆-alkylene-Y—, wherein        -   Y and W² independently of each other are a direct bond,            —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or —O—C(O)—;        -   R¹³ and R¹⁴ independently of each other are selected from            hydrogen, aryl, heteroaryl, C₁₋₆-alkyl, C₁₋₆-alkoxy,            aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-,            aryl-C₁₋₆-alkoxy-, heteroaryl-C₁₋₆-alkoxy-,            C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,            C₁₋₆-alkoxy-heteroarylene-, or C₁₋₆-alkoxy-arylene-;        -   or        -   R₁₃ and R₁₄ may be taken together to form a ring having the            formula —(CH₂)_(o)—X—(CH₂)_(p)— bonded to the nitrogen atom            to which R₁₃ and R₁₄ are attached, wherein            -   o and p are independently of each other are 1, 2, 3, or                4; and            -   X is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—,                —CON(H)—, —NHC(O)—, —NHCON(H)—, —NHSO₂—, —SO₂N(H)—,                —C(O)—O—, —O—C(O)—, —NHSO₂NH—,            -   wherein                -   R¹⁶ and R¹⁷ are selected from hydrogen, aryl,                    heteroaryl, C₁₋₆-alkyl, C₁₋₆-alkoxy,                    aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-,                    C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,                    C₁₋₆-alkoxy-arylene-, C₁₋₆-alkoxy-heteroarylene-,                    heteroarylaryl-C₁₋₆-alkoxy-, or aryl-C₁₋₆-alkoxy-;                    and        -   R¹⁵ is selected from the group consisting of aryl,            heteroaryl, cycloalkyl, heterocyclyl, C₁₋₆-alkyl,            heteroaryl-C₁₋₆-alkylene-, or aryl-C₁₋₆-alkylene-; and    -   R¹² is selected from hydrogen, aryl, heteroaryl, C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-,        C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,        C₁₋₆-alkoxy-heteroarylene-, or C₁₋₆₁-alkoxy-arylene-;        G¹ is C₁₋₆-alkyl, C₃₋₁₀-cycloalkyl,        C₃₋₁₀-cycloalkyl-C₁₋₆-alkylene-, C₂₋₆-alkenyl, or C₂₋₆-alkynyl,        all of which may optionally be substituted with one or more        substituents independently selected from the group consisting of        —CN, —CF₃, —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹, C₃₋₁₀-cycloalkyl and        C₁₋₆-alkyl, wherein    -   R¹⁸ and R¹⁹ independently of each other are hydrogen,        C₁₋₆-alkyl, heteroaryl-C₁₋₆-alkylene-, aryl-C₁₋₆-alkylene-,        C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-, heteroaryl, or        aryl;    -   or    -   R¹⁸ and R¹⁹, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds;        or        G¹ is aryl, heteroaryl, heterocyclyl, fused        cycloalkylheteroaryl, fused heterocyclylaryl, fused        arylheterocyclyl, or fused cycloalkylaryl, all of which may        optionally be substituted with one or more substituents selected        from R⁴⁰, R⁴¹, and R⁴²;        L² is a direct bond, C₁₋₆-alkylene, C₂₋₆-alkenylene,        C₂₋₆-alkynylene, —N(R²⁰)—, —C₁₋₆-alkylene-N(R²⁰)—,        —C₂₋₆-alkenylene-N(R²⁰)—, —C₂₋₆-alkynylene-N(R²⁰)—, wherein    -   R²⁰ is hydrogen, or    -   R²⁰ is C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl, cycloalkyl-W³—,        heterocyclyl-W³—, aryl-W³—, heteroaryl-W³—, optionally        substituted with one or more substituents R³⁰, R³¹, and    -   R³² wherein        -   W³ is C₁₋₆-alkylene or a direct bond;            wherein L¹ and L² are attached to adjacent atoms in A;            L³ is —C(O)—, —C(O)—C(O)—, —C(O)CH₂C(O)— or —S(O)₂—;            R¹ is hydrogen, or            R¹ is C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl,            cycloalkyl-W⁴—, heterocyclyl-W⁴—, aryl-W⁴—, or            heteroaryl-W⁴—,            optionally substituted with one or more substituents R³³,            R³⁴, and R³⁵ wherein    -   W⁴ is C₁₋₆-alkylene or a direct bond;        G² is heteroaryl, fused heterocyclylheteroaryl, or fused        cycloalkylheteroaryl, optionally substituted with one or more        substituents R⁴³, R⁴⁴, and R⁴⁵, wherein said heteroaryl group        possesses a nitrogen atom adjacent to the atom joining said        heteroaryl group to —N(R¹)—;        or a group of the formula        wherein    -   G³ and G⁵ independently of each other are C₁₋₆-alkyl,        C₂₋₆-alkenyl, C₂₋₆-alkynyl, cycloalkyl-R²²—, heterocyclyl-R²²—,        aryl-R²²—, heteroaryl-R²²—, optionally substituted with one or        more substituents R⁴⁶, R⁴⁷, and R⁴⁸, wherein        -   R²² is alkylene or a direct bond; and    -   R²¹ is hydrogen, C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl,        cycloalkyl-W⁵—, or heterocyclyl-W⁵—,    -   optionally substituted with one or more substituents R³⁶, R³⁷,        and R³⁸, or    -   R²¹ is aryl-W⁵—, or heteroaryl-W⁵—, optionally substituted with        one or more substituents R⁴⁹, R⁵⁰, and R⁵¹, wherein        -   W⁵ is C₁₋₆-alkylene or a direct bond;            wherein            R³⁰, R³¹, R³², R³³, R³⁴, R³⁵, R³⁶, R³⁷, and R³⁸            independently of each other are selected from            —CHF₂, —CF₃, —OCF₃, —OCHF₂, —OCH₂CF₃, —OCF₂CHF₂, —S(O)₂CF₃,            —SCF₃, —OR⁵², —NR⁵²R⁵³, —SR₅₂, —NR⁵²S(O)₂R⁵³, —S(O)₂NR⁵²R⁵³,            —S(O)NR⁵²R⁵³, —S(O)R⁵², —S(O)₂R⁵², —C(O)NR⁵²R⁵³,            —OC(O)NR⁵²R⁵³, —NR⁵²C(O)R⁵³, —CH₂C(O)NR⁵²R⁵³,            —OCH₂C(O)NR⁵²R⁵³, —CH₂OR⁵², —CH₂NR⁵²R⁵³, —OC(O)R⁵², —C(O)R⁵²            and —C(O)OR⁵²; or            C₂₋₆-alkenyl and C₂₋₆-alkynyl, which may optionally be            substituted with one or more substituents selected from —CN,            —CF₃, —OCF₃, —OR⁵², —NR⁵²R⁵³ and C₁₋₆-alkyl; or            C₃₋₁₀-cycloalkyl, C₄₋₈-cycloalkenyl, heterocyclyl,            C₃₋₁₀-cycloalkyl-C₁₋₆-alkylene-,            C₃₋₁₀-cycloalkyl-C₁₋₆-alkoxy-, C₃₋₁₀-cycloalkyloxy,            C₃₋₁₀-cycloalkyl-C₁₋₆-alkylthio-, C₃₋₁₀-cycloalkylthio,            C₃₋₁₀-cycloalkyl-C₂₋₆-alkenylene-,            C₃₋₁₀-cycloalkyl-C₂₋₆-alkynylene-,            C₄₋₈-cycloalkenyl-C₁₋₆-alkylene-,            C₄₋₈-cycloalkenyl-C₂₋₆-alkenylene-,            C₄₋₈-cycloalkenyl-C₂₋₆-alkynylene-,            heterocyclyl-C₁₋₆-alkylene-, heterocyclyl-C₂₋₆-alkenylene-,            heterocyclyl-C₂₋₆-alkynylene-, aryl, aryloxy,            aryloxycarbonyl, aroyl, aryl-C₁₋₆-alkoxy-,            aryl-C₁₋₆-alkylene-, aryl-C₂₋₆-alkenylene-,            aryl-C₂₋₆-alkynylene-, heteroaryl,            heteroaryl-C₁₋₆-alkylene-, heteroaryl-C₂₋₆-alkenylene- and            heteroaryl-C₂₋₆-alkynylene-, of which the aryl and            heteroaryl moieties optionally may be substituted with one            or more substituents selected from halogen, —C(O)OR⁵², —CN,            —CF₃, —OCF₃, —NO₂, —OR⁵², —NR⁵²R⁵³ and C₁₋₆-alkyl, wherein    -   R⁵² and R⁵³ independently of each other are hydrogen,        C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene-heteroaryl-C₁₋₆-alkylene-heteroaryl, or aryl;    -   or    -   R⁵² and R⁵³, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds;        R⁴⁰, R⁴¹, R⁴², R⁴³, R⁴⁴, R⁴⁵, R⁴⁶, R⁴⁷, R⁴⁸, R⁴⁹, R⁵⁰ and R⁵¹        independently of each other are —CN, —NO₂, —S(O)₂CF₃, —SCF₃,        —OR⁵⁴, —NR⁵⁴R⁵⁵, —SR⁵⁴, —NR⁵⁴S(O)₂R⁵⁵, —S(O)₂NR⁵⁴R⁵⁵,        —S(O)NR⁵⁴R⁵⁵, —S(O)R⁵⁴, —S(O)₂R⁵⁴, —C(O)NR⁵⁴R⁵⁵, —OC(O)NR⁵⁴R⁵⁵,        —NR⁵⁴C(O)R⁵⁵, halogen, —S—C₁₋₆-alkylene-OR⁵⁴,        —S(O)₂—C₁₋₆-alkylene-OR⁵⁴, —C₁₋₆-alkylene-S—R⁵⁴,        —C₁₋₆-alkylene-S(O)R⁵⁴, —C₁₋₆-alkylene-S(O)₂R⁵⁴,        —C₁₋₆-alkylene-N(R⁵⁴)S(O)₂R⁵⁵, —N(R⁵⁴)S(O)₂R⁵⁵,        —C₁₋₆-alkylene-CN,        —C₁₋₆-alkylene-C(O)NR⁵⁴R⁵⁵, —C₁₋₆-alkylene-N(R⁵⁴)C(O)R⁵⁵,        —N(R⁵⁴)C(O)R⁵⁵, —C₁₋₆-alkylene-N(R⁵⁴)C(O)NR⁵⁵R⁵⁶,        —C₁₋₆-alkylene-NHC(═NR⁵⁴)NR⁵⁵R⁵⁶, —C₁₋₆-alkylene-N(R⁵⁴)C(O)OR⁵⁵,        —N(R⁵⁴)C(O)OR⁵⁵, —C₁₋₆-alkylene-C(O)OR⁵⁴,        —C₁₋₆-alkylene-N(R⁵⁴)S(O)₂R⁵⁵, —OCH₂C(O)NR⁵⁴R⁵⁵, —O(CH₂)₁₋₃OR⁵⁴,        —C₁₋₆-alkylene-O—R⁵⁴, —C₁₋₆-alkylene-C(O)R⁵⁴,        —C₁₋₆-alkylene-NR⁵⁴R⁵⁵, —C(═NR⁵⁴)—O—R⁵⁵, —C(═N(OR⁵⁴))C(O)OR⁵⁵,        —C(═N(OR⁵⁴))C(O)R⁵⁵, —C₁₋₆-alkylene-C(═N(OR⁵⁴))C(O)R⁵⁵,        —C₁₋₆-alkylene=N—O—R⁵⁴, —C₁₋₆-alkylene-N(R⁵⁴)S(O)₂NR⁵⁵R⁵⁶,        —N(R⁵⁴)S(O)₂NR⁵⁵R⁵⁶, —N(R⁵⁴)S(O)₂NR⁵⁵R⁵⁶, —OC(O)R⁵⁴,        —C₁₋₆-alkylene-C(O)N(R⁵⁴)S(O)₂R⁵⁵, —C(O)N(R⁵⁴)S(O)₂R⁵⁵,        —C₁₋₆-alkylene-C(R⁵⁴)═N—OR⁵⁵, —NHC(═NR⁵⁴)NR⁵⁵R⁵⁶,        —C₁₋₆-alkylene-NHC(═NR⁵⁴)NR⁵⁴R⁵⁵,        —C₁₋₆-alkylene-N═C(N(R⁵⁴R⁵⁵))₂, —N═C(N(R⁵⁴R⁵⁵))₂, —C(O)R⁵⁴ and        —C(O)OR⁵⁴; or        C₁₋₆-alkyl, C₂₋₆-alkenyl and C₂₋₆-alkynyl, each of which may        optionally be substituted with one or more substituents        independently selected from halogen, R⁵⁴, —CN, —CF₃, —OCF₃,        —OR⁵⁴, —C(O)OR⁵⁴, —NR⁵⁴R⁵⁵ and C₁₋₆-alkyl; or        C₃₋₁₀-cycloalkyl, C₄₋₈-cycloalkenyl, heterocyclyl,        C₃₋₁₀-cycloalkyl-C₁₋₆-alkylene-, C₃₋₁₀-cycloalkyl-C₁₋₆-alkoxy-,        C₃₋₁₀-cycloalkyloxy, C₃₋₁₀-cycloalkyl-C₁₋₆-alkylthio-,        C₃₋₁₀-cycloalkylthio, C₃₋₁₀-cycloalkyl-C₂₋₆-alkenylene-,        C₃₋₁₀-cycloalkyl-C₂₋₆-alkynylene-,        C₄₋₈-cycloalkenyl-C₁₋₆-alkylene-,        C₄₋₈-cycloalkenyl-C₂₋₆-alkenylene-,        C₄₋₈-cycloalkenyl-C₂₋₆-alkynylene-, heterocyclyl-C₁₋₆-alkylene-,        heterocyclyl-C₂₋₆-alkenylene-, heterocyclyl-C₂₋₆-alkynylene- of        which the heterocyclyl moieties optionally may be substituted        with one or more substituents independently selected from R⁷⁰;        or        aryl, aryloxy, aryloxycarbonyl, aroyl, aryl-C₁₋₆-alkoxy-,        aryl-C₁₋₆-alkylene-, aryl-C₂₋₆-alkenylene-,        aryl-C₂₋₆-alkynylene-, heteroaryl, heteroaryl-C₁₋₆-alkylene-,        heteroaryl-S—C₁₋₆-alkylene-, heteroaryl-C₂₋₆-alkenylene- and        heteroaryl-C₂₋₆-alkynylene-, of which the aryl and heteroaryl        moieties optionally may be substituted with one or more        substituents selected from halogen, —C(O)OR⁵⁴, —CN, —CF₃, —OCF₃,        —NO₂, —OR⁵⁴, —NR⁵⁴R⁵⁵ or C₁₋₆-alkyl, wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are hydrogen,        C₁₋₆-alkyl, —Si(C₁₋₆-alkyl)₃, C₁₋₆-alkyl-arylene-,        C₁₋₆-alkyl-heteroarylene-, aryl-C₁₋₆-alkylene-,        heteroaryl-C₁₋₆-alkylene-, heterocyclyl,        heterocyclyl-C₁₋₆-alkylene-, heteroaryl, or aryl, each of which        is optionally substituted with one or more substituents        independently selected from R⁷¹;    -   or    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen or        —(CHR⁷²)—(CHR⁷³)_(v)W⁶, wherein        -   u is 0, 1 or 2;        -   v is 0, 1 or 2;        -   R⁷² and R⁷³ independently of each other are hydrogen,            C₁₋₆-alkyl, C₁₋₆-alkyl-arylene-aryl, hydroxy, hydroxyalkyl,            —C(O)O—R⁷⁵, amino, or aminoalkyl;        -   W⁶ is hydrogen, —O—R⁷⁵, —C(O)O—R⁷⁵, —C(O)—R⁷⁵, —CONR⁷⁵R⁷⁶,            —NR⁷⁵R⁷⁶, —NHCH₂C(O)R⁷⁵, —NHC(O)R⁷⁵, —NHC(O)OR⁷⁵, —S(O)₂R⁷⁵,            —NHS(O)₂R⁷⁵, alkylamino, or dialkylamino, or        -   W⁶ is a five or six membered ring wherein at least one ring            atom is nitrogen and the remaining ring atoms are either            carbon or oxygen or optionally substituted with C₁₋₆-alkyl,            —C(O)O—R⁷⁵, —(CH₂)₁₋₃C(O)O—R⁷⁵, ═O;        -   or        -   W⁶ is phathalimido or heterocyclyl.    -   or    -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds, and optionally        substituted with one or more C₁₋₆-alkyl groups;    -   R⁷⁰ is ═O, —C(O)CH₃, —S(O)₂CH₃, —CF₃, —C(O)O—R⁷⁵,        —(CH₂)₁₋₃C(O)O—R⁷⁵ or C₁₋₆-alkyl;    -   R⁷¹ is ═O, C₁₋₆-alkyl, cycloalkyl, —C(O)O—R⁷⁵,        —(CH₂)₁₋₃C(O)O—R⁷⁵, —(CH₂)₁₋₃NR⁷⁵R⁷⁵, —OH or amino;    -   R⁷⁵ and R⁷⁶ independently of each other is hydrogen, halogen,        —OH, —CF₃, or C₁₋₆-alkyl optionally substituted with —NH₂;        or a pharmaceutically acceptable salt, solvate, or prodrug        thereof.        Embodiment A2. A compound according to embodiment A1, wherein        A¹ is arylene or heteroarylene, optionally substituted with one        or more substitutents R²³, R²⁴, R²⁵, R²⁵, and R²⁷, wherein    -   R²³, R²⁴, R²⁵, R²⁶, and R²⁷ independently of each other are        selected from the group consisting of    -   halogen, —C(O)OR², —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³,        C₁₋₆-alkyl-Z-, C₂₋₆-alkenyl-Z-, C₂₋₆-alkynyl-Z-, cycloalkyl-Z-,        heterocyclyl-Z-, aryl-Z-, heteroaryl-Z-, aryl-C₁₋₆-alkylene-Z-,        heteroaryl-C₁₋₆-alkylene-Z-, heterocyclyl-C₁₋₆-alkylene-Z-,        cycloalkyl-C₁₋₆-alkylene-Z-, N(R⁴R⁵)—C₁₋₆-alkylene-Z-, R⁶—W¹-Z-,        R⁶—W¹—N(R⁴)-Z-, R⁶—N(R⁴)-Z, and R⁶—W¹—C₁₋₆-alkylene-Z-, wherein        -   R², R³, R⁴, R⁵, R⁶, Z, and W¹ are as defined in embodiment            A1.            Embodiment A3. A compound according to embodiment A2,            wherein            A¹ is C₆₋₁₀-arylene or C₄₋₁₀-heteroarylene, optionally            substituted with one or more substitutents R²³, R²⁴, R²⁵,            R²⁶, and R²⁷, wherein    -   R²³, R²⁴, R²⁵, R²⁶, and R²⁷ independently of each other are        selected from the group consisting of    -   halogen, —C(O)OR², —CN; —CF₃, —OCF₃, —NO₂, —OR², —NR²R³,        C₁₋₆-alkyl-Z-, C₂₋₆-alkenyl-Z-, C₂₋₆-alkynyl-Z-, cycloalkyl-Z-,        heterocyclyl-Z-, aryl-Z-, heteroaryl-Z-, aryl-C₁₋₆-alkylene-Z-,        heteroaryl-C₁₋₆-alkylene-Z-, heterocyclyl-C₁₋₆-alkylene-Z-,        cycloalkyl-C₁₋₆-alkylene-Z-, N(R⁴R⁵)—C₁₋₆-alkylene-Z-, R⁶—W¹-Z-,        R⁶—W¹—N(R⁴)-Z-, R⁶—N(R⁴)-Z, and R⁶—W¹—C₁₋₆-alkylene-Z-, wherein        -   R², R³, R⁴, R⁵, R⁶, Z, and W¹ are as defined in embodiment            A1.            Embodiment A4. A compound according to embodiment A3 wherein            A¹ is phenylene optionally substituted with one or more            substitutents R²³, R²⁴, R²⁵, R²⁶, and R²⁷, wherein    -   R²³, R²⁴, R²⁵, R²⁶, and R²⁷ independently of each other are        selected from the group consisting of    -   halogen, —C(O)OR², —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³,        C₁₋₆-alkyl-Z-, C₂₋₆-alkenyl-Z-, C₂₋₆-alkynyl-Z-, cycloalkyl-Z-,        heterocyclyl-Z-, aryl-Z-, heteroaryl-Z-, aryl-C₁₋₆-alkylene-Z-,        heteroaryl-C₁₋₆-alkylene-Z-, heterocyclyl-C₁₋₆-alkylene-Z-,        cycloalkyl-C₁₋₆-alkylene-Z-, N(R⁴R⁵)—C₁₋₆-alkylene-Z-, R⁶—W¹-Z-,        R⁶—W¹—N(R⁴)-Z-, R⁶—N(R⁴)-Z, and R⁶—W¹—C₁₋₆-alkylene-Z-, wherein        R², R³, R⁴, R⁵, R⁶, Z, and W¹ are as defined in embodiment A1.        Embodiment A5. A compound according to embodiment A4 of the        formula (Ia)        wherein L¹, G¹, L², L³, R¹, G² and R²⁵ are as defined in        embodiment A1.        Embodiment A6. A compound according to embodiment A4 of the        formula (Ib)        wherein L¹, G¹, L², L³, R¹, G² and R²⁴ are as defined in        embodiment A1.        Embodiment A7. A compound according to any one of the        embodiments A1 to A6, wherein    -   R²³, R²⁴, R²⁵, R²⁶, and R²⁷ independently of each other are        selected from the group consisting of    -   halogen, —C(O)OR², —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³,        C₁₋₆-alkyl-Z-, cycloalkyl-Z-, heterocyclyl-Z-, aryl-Z-, or        heteroaryl-Z-, N(R⁴R⁵)—C₁₋₆-alkylene-Z-, R⁶—W¹-Z-,        R⁶—W¹—N(R⁴)-Z-, R⁶—N(R⁴)-Z, and R⁶—W¹—C₁₋₆-alkylene-Z-, wherein        -   R², R³, R⁴, R⁵, R⁶, Z, and W¹ are as defined in embodiment            A1.            Embodiment A8. A compound according to embodiment A7 wherein    -   R²³, R²⁴, R²⁵, R²⁶, and R²⁷ independently of each other are        selected from the group consisting of    -   halogen, —CN, —CF₃, —OR², —NR²R³, C₁₋₆-alkyl-Z-, cycloalkyl-Z-,        heterocyclyl-Z-, aryl-Z-, or heteroaryl-Z-, R⁶—W¹-Z-,        R⁶—W¹—N(R⁴)-Z-, R⁶—N(R⁴)-Z, and R⁶—W¹—C₁₋₆-alkylene-Z-, wherein        -   R², R³, R⁴, R⁵, R⁶, Z, and W¹ are as defined in embodiment            A1.            Embodiment A9. a compound according to embodiment A8 wherein    -   R²³, R²⁴, R²⁵, R²⁶, and R²⁷ independently of each other are        selected from the group consisting of    -   halogen, —OR², —NR²R³, C₁₋₆-alkyl-Z-, R⁶—W¹-Z-, and        R⁶—W¹—C₁₋₆-alkylene-Z-, wherein        -   R², R³, R⁴, R⁵, R⁶, Z, and W¹ are as defined in embodiment            A1.            Embodiment A10. A compound according to embodiment A9            wherein    -   R²³, R²⁴, R²⁵, R²⁶, and R²⁷ independently of each other are        selected from the group consisting of        -   F, Cl, Br, and methyl.            Embodiment A11. A compound according to any one of the            embodiments A1 to A10, wherein    -   R⁴, R⁵, and R⁶ independently of each other are selected from the        group consisting of    -   hydrogen, aryl, C₁₋₆-alkyl, heteroaryl-C₁₋₆-alkylene-, and        aryl-C₁₋₆-alkylene-.        Embodiment A12. A compound according to embodiment A11, wherein    -   R⁴, R⁵, and R⁶ independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment A13. A compound according to embodiment A12, wherein    -   R⁴, R⁵, and R⁶ are hydrogen.        Embodiment A14. A compound according to any one of the        embodiments A1 to A9, wherein    -   R⁴ and R⁵ is taken together to form a ring having the formula        —(CH₂)_(j)-Q-(CH₂)_(k)— bonded to the nitrogen atom to which R⁴        and R⁵ are attached, wherein        -   j and k independently of each other is 1, 2, 3, or 4;        -   Q is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—,            —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —NHSO₂—, —SO₂NH—, —C(O)—O—,            —O—C(O)—, —NHSO₂NH—,        -   wherein            -   R⁹ and R¹⁰ independently of each other are selected from                the group consisting of hydrogen, aryl, C₁₋₆-alkyl, and                aryl-C₁₋₆-alkyl-.                Embodiment A15. A compound according to embodiment A14,                wherein    -   Q is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—, —C(O)NH—,        —NHC(O)—, —NHC(O)NH—, —NHSO₂—, —SO₂NH—, —C(O)—O—, —O—C(O)—,        —NHSO₂NH—,    -   wherein        -   R⁹ and R¹⁰ independently of each other are hydrogen or            C₁₋₆-alkyl.            Embodiment A16. A compound according to embodiment A15,            wherein    -   Q is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—, —C(O)NH—,        —NHC(O)—, —NHC(O)NH—, —NHSO₂—, —SO₂NH—, —C(O)—O—, —O—C(O)—,        —NHSO₂NH—,        Embodiment A17. A compound according to embodiment A16, wherein        Q is a direct bond.        Embodiment A18. A compound according to any one of the        embodiments A1 to A17, wherein    -   W¹ is a direct bond, —O—, —C(O)—, —NH—, —S—, —SO₂—, —C(O)NH—,        —NHC(O)—, —N(H)CON(H)—, —N(H)SO₂—, —SO₂N(H)—, —C(O)—O—,        —N(H)SO₂N(H)—, or —O—C(O)—.        Embodiment A19. A compound according to embodiment A18, wherein    -   W¹ is a direct bond, —O—, —C(O)—, —SO₂—, —C(O)NH—, —NHC(O)—,        —N(H)SO₂—, —C(O)—O—, or —O—C(O)—.        Embodiment A20. A compound according to embodiment A19, wherein        W¹ is a direct bond or —C(O)—O—.        Embodiment A21. A compound according to embodiment A20, wherein        W¹ is a direct bond.        Embodiment A22. A compound according to embodiment A7, wherein    -   at least one of R²³, R²⁴, R²⁵, R²⁶, and R²⁷ is halogen,        —C(O)OR², —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³, C₁₋₆-alkyl-Z-,        cycloalkyl-Z-, heterocyclyl-Z-, aryl-Z-, or heteroaryl-Z-,        wherein        -   R², R³, and Z are as defined in embodiment A1.            Embodiment A23. A compound according to embodiment A22,            wherein    -   at least one of R²³, R²⁴, R²⁵, R²⁶, and R²⁷ is halogen,        —C(O)OR², —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³, C₁₋₆-alkyl-Z-,        C₃₋₁₀-cycloalkyl-Z-, C₃₋₁₀-heterocyclyl-Z-, C₃₋₁₀-aryl-Z-, or        C₃₋₁₀-heteroaryl-Z-, wherein        -   R², R³, and Z are as defined in embodiment A1.            Embodiment A24. A compound according to embodiment A23,            wherein    -   at least one of R²³, R²⁴, R²⁵, R²⁶, and R²⁷ is halogen,        —C(O)OR², —CN, —NO₂, —OR², —NR²R³, C₁₋₆-alkyl-Z-,        C₃₋₁₀-cycloalkyl-Z-, C₃₋₁₀-heterocyclyl-Z-, C₃₋₁₀-aryl-Z-, or        C₃₋₁₀-heteroaryl-Z-, wherein        -   R², R³, and Z are as defined in embodiment A1.            Embodiment A25. A compound according to embodiment A24,            wherein    -   at least one of R²³, R²⁴, R²⁵, R²⁶, and R²⁷ is F, Cl, Br, or        methyl.        Embodiment A26. A compound according to embodiment A24, wherein    -   at least one of R²³, R²⁴, R²⁵, R²⁶, and R²⁷ is halogen,        —C(O)OR², —CN, —NO₂, —OR², or —NR²R³, wherein        -   R², R³, and Z are as defined in embodiment A1.            Embodiment A27. A compound according to any one of the            embodiments A1 to A26, wherein    -   R² and R³ independently of each other are hydrogen, C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-,        C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-, heteroaryl, or        aryl.        Embodiment A28. A compound according to embodiment A27, wherein    -   R² and R³ independently of each other, are hydrogen, C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene- or aryl.        Embodiment A29. A compound according to embodiment A28, wherein    -   R² is hydrogen or C₁₋₆-alkyl.        Embodiment A30. A compound according to embodiment A29, wherein    -   R² is hydrogen.        Embodiment A31. A compound according to any one of the        embodiments A1 to A30, wherein    -   R³ is hydrogen or C₁₋₆-alkyl.        Embodiment A32. A compound according to embodiment A31, wherein    -   R³ is hydrogen.        Embodiment A33. A compound according to any one of the        embodiments A1 to A22, wherein    -   R² and R³, when attached to the same nitrogen atom, together        with said nitrogen atom may form a 3 to 8 membered heterocyclic        ring optionally containing one or two further heteroatoms        selected from nitrogen, oxygen and sulfur, and optionally        containing one or two double bonds.        Embodiment A34. A compound according to any one of the        embodiments A1 to A33, wherein    -   Z is a direct bond, —O—, —NH—, —NHCH₂—, —S—, —SO₂—, —C(O)NH—,        —NHC(O)—, —N(H)CON(H)—, —N(CH₃)CONH—, —N(H)SO₂—, —SO₂N(H)—,        —C(O)—O—, —N(H)SO₂N(H)—, or —O—C(O)—.        Embodiment A35. A compound according to embodiment A34, wherein    -   Z is a direct bond, —O—, —S—, —SO₂—, —C(O)NH—, —NHC(O)—,        —N(H)SO₂—, —C(O)—O—, —N(H)SO₂N(H)—, or —O—C(O)—.        Embodiment A36. A compound according to embodiment A35, wherein    -   Z is a direct bond, —NHC(O)—, or —NHS(O)₂—.        Embodiment A37. A compound according to embodiment A2, wherein        A¹ is        R²³, R²⁴, R²⁵, and R²⁶, independently of each other, are        hydrogen or as defined in embodiment A1.        Embodiment A38. A compound according to embodiment A37, wherein    -   R²³, R²⁴, R²⁵, and R²⁶ independently of each other are selected        from the group consisting of    -   halogen, —C(O)OR², —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³,        C₁₋₆-alkyl-Z-, cycloalkyl-Z-, heterocyclyl-Z-, aryl-Z-, or        heteroaryl-Z-, N(R⁴R⁵)—C₁₋₆-alkylene-Z-, R⁶—W¹-Z-,        R⁶—W¹—N(R⁴)-Z-, R⁶—N(R⁴)-Z-, and R⁶—W¹—C₁₋₆-alkylene-Z-, wherein        -   R², R³, R⁴, R⁵, R⁶, Z, and W¹ are as defined in embodiment            A1.            Embodiment A39. A compound according to embodiment A37 or            A38, wherein    -   R⁴, R⁵, and R⁶ independently of each other are selected from the        group consisting of    -   hydrogen, aryl, C₁₋₆-alkyl, heteroaryl-C₁₋₆-alkylene-, and        aryl-C₁₋₆-alkylene-.        Embodiment A40. A compound according to embodiment A39, wherein    -   R⁴, R⁵, and R⁶ independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment A41. A compound according to embodiment A40, wherein    -   R⁴, R⁵, and R⁶ are hydrogen.        Embodiment A42. A compound according to embodiment A37 or A38,        wherein    -   R⁴ and R⁵ is taken together to form a ring having the formula        —(CH₂)_(j)-Q-(CH₂)_(k)— bonded to the nitrogen atom to which R⁴        and R⁵ are attached, wherein        -   j and k independently of each other is 1, 2, 3, or 4;        -   Q is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—,            —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —NHSO₂—, —SO₂NH—, —C(O)—O—,            —O—C(O)—, —NHSO₂NH—,        -   wherein            -   R⁹ and R¹⁰ independently of each other are selected from                the group consisting of hydrogen, aryl, C₁₋₆-alkyl, and                arylalkyl-.                Embodiment A43. A compound according to embodiment A42,                wherein    -   Q is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—, —C(O)NH—,        —NHC(O)—, —NHC(O)NH—, —NHSO₂—, —SO₂NH—, —C(O)—O—, —O—C(O)—,        —NHSO₂NH—,    -   wherein        -   R⁹ and R¹⁰ independently of each other are hydrogen or            alkyl.            Embodiment A44. A compound according to embodiment A43,            wherein    -   Q is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—, —C(O)NH—,        —NHC(O)—, —NHC(O)NH—, —NHSO₂—, —SO₂NH—, —C(O)—O—, —O—C(O)—,        —NHSO₂NH—,        Embodiment A45. A compound according to embodiment A44, wherein    -   Q is a direct bond.        Embodiment A46. A compound according to any one of the        embodiments A37 to A45, wherein    -   W¹ is a direct bond, —O—, —C(O)—, —NH—, —S—, —SO₂—, —C(O)NH—,        —NHC(O)—, —N(H)CON(H)—, —N(H)SO₂—, —SO₂N(H)—, —C(O)—O—,        —N(H)SO₂N(H)—, or —O—C(O)—.        Embodiment A47. A compound according to embodiment A46 wherein    -   W¹ is a direct bond, —O—, —C(O)—, —SO₂—, —C(O)NH—, —NHC(O)—,        —N(H)SO₂—, —C(O)—O—, or —O—C(O)—.        Embodiment A48. A compound according to embodiment A47, wherein    -   W¹ is a direct bond, or —C(O)—O—.        Embodiment A49. A compound according to embodiment A48, wherein    -   W¹ is a direct bond.        Embodiment A50. A compound according to embodiment A37, wherein    -   at least one of R²³, R²⁴, R²⁵, and R²⁶ is halogen, —C(O)OR²,        —CN, —CF₃, —OCF₃, —NO₂, —OR², —NR²R³, C₁₋₆-alkyl-Z-,        cycloalkyl-Z-, heterocyclyl-Z-, aryl-Z-, or heteroaryl-Z-,        wherein        -   R², R³, and Z are as defined in embodiment A37.            Embodiment A51. A compound according to embodiment A50,            wherein    -   at least one of R²³, R²⁴, R²⁵, and R²⁵ is halogen, —C(O)OR²,        —CN, —CF₃, —OCF₃, —N₂, —OR², —NR²R³, C₁₋₆-alkyl-Z-,        C₃₋₁₀-cycloalkyl-Z-, C₃₋₁₀-heterocyclyl-Z-, C₃₋₁₀-aryl-Z-, or        C₃₋₁₀-heteroaryl-Z-, wherein        -   R², R³, and Z are as defined in embodiment A37.            Embodiment A52. A compound according to embodiment A51,            wherein    -   at least one of R²³, R²⁴, R²⁵, and R²⁶ is halogen, —C(O)OR²,        —CN, —NO₂, —OR², —NR²R³, C₁₋₆-alkyl-Z-, C₃₋₁₀-cycloalkyl-Z-,        C₃₋₁₀-heterocyclyl-Z-, C₃₋₁₀-aryl-Z-, or C₃₋₁₀-heteroaryl-Z-,        wherein        -   R², R³, and Z are as defined in embodiment A37.            Embodiment A53. A compound according to any one of the            embodiments A37 to A52, wherein    -   Z is a direct bond, —O—, —NH—, —NHCH₂—, —S—, —SO₂—, —C(O)NH—,        —NHC(O)—, —N(H)CON(H)—, —N(CH₃)CON(H)—, —N(H)SO₂—, —SO₂N(H)—,        —C(O)—O—, —N(H)SO₂N(H)—, or —O—C(O)—.        Embodiment A54. A compound according to embodiment A53, wherein    -   Z is a direct bond, —O—, —S—, —SO₂—, —C(O)NH—, —NHC(O)—,        —N(H)SO₂—, —C(O)—O—, —N(H)SO₂N(H)—, or —O—C(O)—.        Embodiment A55. A compound according to embodiment A54, wherein    -   Z is a direct bond, —NHC(O)—, or —NHS(O)₂.        Embodiment A56. A compound according to embodiment A52, wherein    -   at least one of R²³, R²⁴, R²⁵, and R²⁶ is halogen, —C(O)OR²,        —CN, —NO₂, —OR², —NR²R³, or C₁₋₆-alkyl, wherein        -   R², and R³ are as defined in embodiment A37.            Embodiment A57. A compound according to any one of the            embodiments A37 to A56, wherein    -   R² and R³ independently of each other are hydrogen, C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-,        C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-, heteroaryl, or        aryl.        Embodiment A58. A compound according to embodiment A57, wherein    -   R² and R³ independently of each other, are hydrogen, C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene- or aryl.        Embodiment A59. A compound according to embodiment A58, wherein    -   R² is hydrogen or C₁₋₆-alkyl.        Embodiment A60. A compound according to embodiment A59, wherein    -   R² is hydrogen.        Embodiment A61. A compound according to any one of the        embodiments A37 to A60, wherein    -   R³ is hydrogen or C₁₋₆-alkyl.        Embodiment A62. A compound according to embodiment A61, wherein    -   R³ is hydrogen.        Embodiment A63. A compound according to any one of the        embodiments A37 to A50, wherein    -   R² and R³, when attached to the same nitrogen atom, together        with said nitrogen atom may form a 3 to 8 membered heterocyclic        ring optionally containing one or two further heteroatoms        selected from nitrogen, oxygen and sulfur, and optionally        containing one or two double bonds.        Embodiment A64. A compound according to any one of the        embodiments A37 to A55, wherein    -   at least one of R²³, R²⁴, R²⁵, and R²⁶ are hydrogen.        Embodiment A65. A compound according to embodiment A64, wherein    -   at least two of R²³, R²⁴, R²⁵, and R²⁶ are hydrogen.        Embodiment A66. A compound according to embodiment A65, wherein    -   R²³ and R²⁶ are hydrogen.        Embodiment A67. A compound according to embodiment A65 or        embodiment A66, wherein    -   at least three of R²³, R²⁴, R²⁵, and R²⁶ are hydrogen.        Embodiment A68. A compound according to any one of the        embodiments A37 to A67, wherein R²⁴ or R²⁵ is halogen.        69. A compound according to embodiment A68, wherein R²⁴ or R²⁵        is fluoro.        Embodiment A70. A compound according to any one of the        embodiments A37 to A67, wherein R²⁴ or R²⁵ is C₁₋₆-alkyl.        Embodiment A71. A compound according to embodiment A68, wherein        R²⁴ or R²⁵ is methyl.        Embodiment A72. A compound according to any one of the        embodiments A37 to A67, wherein    -   R²⁴ is hydrogen.        Embodiment A73. A compound according to any one of the        embodiments A37 to A72, wherein    -   R²⁵ is hydrogen.        Embodiment A74. A compound according to embodiment A37, wherein    -   R²³, R²⁴, R²⁵, and R²⁶ are hydrogen.        Embodiment A75. A compound according to any one of the        embodiments A1 to A74, wherein    -   L¹ is a bond, -D-alkylene-E-, —O—, —S—, —S(O)—, —S(O)₂—, —C(O)—,        —N(R¹¹)—, or —C(═N—OR¹²), wherein        -   D, E, R¹¹ and R¹² are as defined in embodiment A1.            Embodiment A76. A compound according to embodiment A75,            wherein    -   L¹ is a bond, -D-alkylene-E-, —O—, —C(O)—, —N(R¹¹)—, or        —C(═N—OR¹²)—, wherein        -   D, E, R¹¹ and R¹² are as defined in embodiment A1.            Embodiment A77. A compound according to embodiment A75,            wherein    -   L¹ is —O—.        Embodiment A78. A compound according to embodiment A75, wherein    -   L¹ is —S—.        Embodiment A79. A compound according to embodiment A75, wherein    -   L¹ is a bond.        80. A compound according to embodiment A75, wherein    -   L¹ is —C(O)—.        Embodiment A81. A compound according to any one of the        embodiments A1 to A76, wherein    -   D is a direct bond or —O—;    -   E is a direct bond or —O—; and    -   R¹¹ and R¹² are as defined in embodiment A1.        Embodiment A82. A compound according to embodiment A81, wherein    -   D is a direct bond.        Embodiment A83. A compound according to embodiment A81, wherein    -   D is —O—.        Embodiment A84. A compound according to any one of the        embodiments A81 to A83, wherein    -   E is a direct bond.        Embodiment A85. A compound according to any one of the        embodiments A81 to A83, wherein    -   E is —O—.        Embodiment A86. A compound according to any one of the        embodiments A1 to A85, wherein    -   R¹¹ is selected from hydrogen, C₁₋₆-alkyl, aryl, carbamoyl,        aryl-C₁₋₆-alkylene-, C₁₋₆-alkyl-NH—C(O)—,        aryl-C₁₋₆-alkylene-NH—C(O)—, C₁₋₆-alkyl-SO₂—,        aryl-C₁₋₆-alkylene-SO₂—, aryl-SO₂—, SO₂—, C₁₋₆-alkyl-C(O)—,        aryl-C₁₋₆-alkylene-C(O)—, N(R¹³)(R¹⁴)—C₁₋₆-alkylene-Y—, and        R¹⁵—W²—C₁₋₆-alkylene-Y—, wherein        -   Y and W² independently of each other are a direct bond,            —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or —O—C(O)—;        -   R¹³ and R¹⁴ independently of each other are selected from            hydrogen, aryl, C₁₋₆-alkyl, or aryl-C₁₋₆-alkylene-;        -   or        -   R¹³ and R¹⁴ may be taken together to form a ring having the            formula —(CH₂)_(o)—X—(CH₂)_(p)— bonded to the nitrogen atom            to which R¹³ and R¹⁴ are attached, wherein            -   o and p are independently of each other are 1, 2, 3, or                4; and            -   X is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—,                —CON(H)—, —NHC(O)—, —NHCON(H)—, —NHSO₂—, —SO₂N(H)—,                —C(O)—O—, —O—C(O)—, —NHSO₂NH—,            -   wherein                -   R¹⁶ and R¹⁷ are selected from hydrogen, aryl,                    heteroaryl, C₁₋₆-alkyl, C₁₋₆-alkoxy,                    aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-,                    C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,                    C₁₋₆-alkoxy-arylene-, C₁₋₆-alkoxy-heteroarylene-,                    heteroarylaryl-C₁₋₆-alkoxy-, or aryl-C₁₋₆-alkoxy-;                    and    -   R¹⁵ is selected from the group consisting of aryl, heteroaryl,        cycloalkyl, heterocyclyl, C₁₋₆-alkyl, or aryl-C₁₋₆-alkylene-.        Embodiment A87. A compound according to embodiment A86, wherein    -   R¹¹ is selected from hydrogen, C₁₋₆-alkyl, aryl, carbamoyl,        aryl-C₁₋₆-alkylene-, C₁₋₆-alkyl-NH—C(O)—,        aryl-C₁₋₆-alkylene-NH—C(O)—, C₁₋₆-alkyl-SO₂—,        aryl-C₁₋₆-alkylene-SO₂—, aryl-SO₂—, SO₂—, C₁₋₆-alkyl-C(O)—,        aryl-C₁₋₆-alkylene-C(O)—, N(R¹³)(R¹⁴)—C₁₋₆-alkylene-Y—, and        R¹⁵—W²—C₁₋₆-alkylene-Y—, wherein        -   Y and W² independently of each other are a direct bond,            —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or —O—C(O)—;        -   R¹³ and R¹⁴ independently of each other are selected from            hydrogen, aryl, C₁₋₆-alkyl, or aryl-C₁₋₆-alkylene-;        -   or        -   R¹³ and R¹⁴ may be taken together to form a ring having the            formula —(CH₂)_(o)—X—(CH₂)_(p)— bonded to the nitrogen atom            to which R¹³ and R¹⁴ are attached, wherein            -   o and p are independently of each other are 1, 2, 3, or                4; and            -   X is a direct bond, —CH₂—, —O—, —S—, —S(O₂)—, —C(O)—,                —CON(H)—, —NHC(O)—, —NHCON(H)—, —NHSO₂—, —SO₂N(H)—,                —C(O)—O—, —O—C(O)—,            -   wherein                -   R¹⁶ and R¹⁷ are hydrogen; and    -   R¹⁵ is selected from the group consisting of aryl, heteroaryl,        cycloalkyl, heterocyclyl, C₁₋₆-alkyl, or aryl-C₁₋₆-alkylene-.        Embodiment A88. A compound according to embodiment A87, wherein    -   R¹¹ is selected from hydrogen, C₁₋₆-alkyl, aryl, carbamoyl,        aryl-C₁₋₆-alkylene-, C₁₋₆-alkyl-NH—C(O)—,        aryl-C₁₋₆-alkylene-NH—C(O)—, C₁₋₆-alkyl-SO₂—,        aryl-C₁₋₆-alkylene-SO₂—, aryl-SO₂—, SO₂—, C₁₋₆-alkyl-C(O)—,        aryl-C₁₋₆-alkylene-C(O)—, N(R¹³)(R¹⁴)—C₁₋₆-alkylene-Y—, and        R¹⁵—W²—C₁₋₆-alkylene-Y—, wherein        -   Y and W² independently of each other are a direct bond,            —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or —O—C(O)—;        -   R¹³ and R¹⁴ independently of each other are selected from            hydrogen, aryl, C₁₋₆-alkyl, or aryl-C₁₋₆-alkylene-;        -   or        -   R¹³ and R¹⁴ may be taken together to form a ring having the            formula —(CH₂)_(o)—X—(CH₂)_(p)— bonded to the nitrogen atom            to which R¹³ and R¹⁴ are attached, wherein            -   o and p are independently of each other are 1, 2, 3, or                4;            -   X is a direct bond; and    -   R¹⁵ is selected from the group consisting of aryl, heteroaryl,        cycloalkyl, heterocyclyl, C₁₋₆-alkyl, or aryl-C₁₋₆-alkylene-.        Embodiment A89. A compound according to embodiment A88, wherein    -   R¹¹ is selected from hydrogen, C₁₋₆-alkyl, aryl, carbamoyl,        aryl-C₁₋₆-alkylene-, C₁₋₆-alkyl-NH—C(O)—,        aryl-C₁₋₆-alkylene-NH—C(O)—, C₁₋₆-alkyl-SO₂—,        aryl-C₁₋₆-alkylene-SO₂—, aryl-SO₂—, SO₂—, C₁₋₆-alkyl-C(O)—,        aryl-C₁₋₆-alkylene-C(O)—, N(R¹³)(R¹⁴)—C₁₋₆-alkylene-Y—, and        R¹⁵—W²—C₁₋₆-alkylene-Y—, wherein        -   Y and W² independently of each other are a direct bond,            —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or —O—C(O)—;        -   R¹³ and R¹⁴ independently of each other are selected from            hydrogen, aryl, C₁₋₆-alkyl, or aryl-C₁₋₆-alkylene-; and        -   R¹⁵ is selected from the group consisting of aryl,            heteroaryl, cycloalkyl, heterocyclyl, C₁₋₆-alkyl, or            aryl-C₁₋₆-alkylene-.            Embodiment A90. A compound according to embodiment A89,            wherein    -   R¹¹ is selected from hydrogen, C₁₋₆-alkyl, aryl, carbamoyl,        aryl-C₁₋₆-alkylene-, C₁₋₆-alkyl-NH—C(O)—,        aryl-C₁₋₆-alkylene-NH—C(O)—, C₁₋₆-alkyl-SO₂—,        aryl-C₁₋₆-alkylene-SO₂—, aryl-SO₂—, SO₂—, C₁₋₆-alkyl-C(O)—,        aryl-C₁₋₆-alkylene-C(O)—, N(R¹³)(R¹⁴)—C₁₋₆-alkylene-Y—, and        R¹⁵—W²—C₁₋₆-alkylene-Y—, wherein        -   Y and W² independently of each other are a direct bond,            —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or —O—C(O)—;        -   R¹³ and R¹⁴ are hydrogen; and        -   R¹⁵ is selected from the group consisting of aryl,            heteroaryl, cycloalkyl, heterocyclyl, C₁₋₆-alkyl, or            aryl-C₁₋₆-alkylene-.            Embodiment A91. A compound according to embodiment A90,            wherein    -   R¹¹ is selected from hydrogen, C₁₋₆-alkyl, aryl, carbamoyl,        aryl-C₁₋₆-alkylene-, C₁₋₆-alkyl-NH—C(O)—,        aryl-C₁₋₆-alkylene-NH—C(O)—, C₁₋₆-alkyl-SO₂—,        aryl-C₁₋₆-alkylene-SO₂—, aryl-SO₂—, SO₂—, C₁₋₆-alkyl-C(O)—,        aryl-C₁₋₆-alkylene-C(O)—, N(R¹³)(R¹⁴)—C₁₋₆-alkylene-Y—, and        R¹⁵—W²—C₁₋₆-alkylene-Y—, wherein        -   Y is a direct bond;        -   W² is a direct bond, —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or            —O—C(O)—;        -   R¹³ and R¹⁴ are hydrogen; and            -   R¹⁵ is selected from the group consisting of aryl,                heteroaryl, cycloalkyl, heterocyclyl, C₁₋₆-alkyl, or                aryl-C₁₋₆-alkylene-.                Embodiment A92. A compound according to embodiment A90,                wherein    -   R¹¹ is selected from hydrogen, C₁₋₆-alkyl, aryl, carbamoyl,        aryl-C₁₋₆-alkylene-, C₁₋₆-alkyl-NH—C(O)—,        aryl-C₁₋₆-alkylene-NH—C(O)—, C₁₋₆-alkyl-SO₂—,        aryl-C₁₋₆-alkylene-SO₂—, aryl-SO₂—, SO₂—, C₁₋₆-alkyl-C(O)—,        aryl-C₁₋₆-alkylene-C(O)—, N(R¹³)(R¹⁴)—C₁₋₆-alkylene-Y—, and        R¹⁵—W²—C₁₋₆-alkylene-Y—, wherein        -   Y is a direct bond, —CH₂—, —SO₂—, —N(H)CO—, —N(H)SO₂—, or            —O—C(O)—;        -   W² is a direct bond;        -   R¹³ and R¹⁴ are hydrogen; and        -   R¹⁵ is selected from the group consisting of aryl,            heteroaryl, cycloalkyl, heterocyclyl, C₁₋₆-alkyl, or            aryl-C₁₋₆-alkylene-.            Embodiment A93. A compound according to any one of the            embodiments A90 to A92, wherein    -   R¹¹ is selected from hydrogen, C₁₋₆-alkyl, aryl, carbamoyl,        aryl-C₁₋₆-alkylene-, C₁₋₆-alkyl-NH—C(O)—,        aryl-C₁₋₆-alkylene-NH—C(O)—, C₁₋₆-alkyl-SO₂—,        aryl-C₁₋₆-alkylene-SO₂—, aryl-SO₂—, SO₂—, C₁₋₆-alkyl-C(O)—,        aryl-C₁₋₆-alkylene-C(O)—, NH₂—C₁₋₆-alkylene-, and        R¹⁵—C₁₋₆-alkylene-, wherein        -   R¹⁵ is selected from the group consisting of aryl,            heteroaryl, cycloalkyl, heterocyclyl, C₁₋₆-alkyl, or            aryl-C₁₋₆-alkylene-.            Embodiment A94. A compound according to embodiment A93,            wherein    -   R¹¹ is selected from hydrogen, C₁₋₆-alkyl, aryl, carbamoyl,        aryl-C₁₋₆-alkylene-, C₁₋₆-alkyl-NH—C(O)—,        aryl-C₁₋₆-alkylene-NH—C(O)—, C₁₋₆-alkyl-SO₂—,        aryl-C₁₋₆-alkylene-SO₂—, aryl-SO₂—, SO₂—, C₁₋₆-alkyl-C(O)—,        aryl-C₁₋₆-alkylene-C(O)—, and NH₂—C₁₋₆-alkylene-.        Embodiment A95. A compound according to embodiment A94, wherein    -   R¹¹ is hydrogen or C₁₋₆-alkyl.        Embodiment A96. A compound according to embodiment A95, wherein    -   R¹¹ is hydrogen.        Embodiment A97. A compound according to any one of the        embodiments A1 to A96, wherein    -   R¹² is hydrogen or C₁₋₆-alkyl.        Embodiment A98. A compound according to embodiment A97, wherein    -   R¹² is hydrogen.        Embodiment A99. A compound according to any one of the        embodiments A1 to A98, wherein    -   G¹ is C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl, cycloalkyl or        heterocyclyl, optionally substituted with one or more        substituents selected from the group consisting of —CN, —CF₃,        —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹, C₃₋₁₀-cycloalkyl and C₁₋₆-alkyl, wherein        -   R¹⁸ and R¹⁹ are as defined in embodiment A1.            Embodiment A100. A compound according to embodiment A99,            wherein    -   G¹ is C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl, cycloalkyl or        heterocyclyl, optionally substituted with one or more        substituents selected from the group consisting of —CN, —CF₃,        —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹ and C₁₋₆-alkyl, wherein        -   R¹⁸ and R¹⁹ are as defined in embodiment A1.            Embodiment A101. A compound according to embodiment A99,            wherein    -   G¹ is C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl, C₃₋₁₀-cycloalkyl        or C₃₋₁₀-heterocyclyl, optionally substituted with one or more        substituents selected from the group consisting of —CN, —CF₃,        —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹, C₃₋₁₀-cycloalkyl and C₁₋₆-alkyl, wherein        -   R¹⁸ and R¹⁹ are as defined in embodiment A1.            Embodiment A102. A compound according to embodiment A100 or            embodiment A101, wherein    -   G¹ is C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl, C₃₋₁₀-cycloalkyl        or C₃₋₁₀-heterocyclyl, optionally substituted with one or more        substituents selected from the group consisting of —CN, —CF₃,        —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹ and C₁₋₆-alkyl, wherein        -   R¹⁸ and R¹⁹ are as defined in embodiment A1.            Embodiment A103. A compound according to any one of the            embodiments A99 to A102, wherein    -   G¹ is selected from the group consisting of methyl, ethyl,        propyl, butyl, isopropyl, isobutyl, sec-butyl, tert-butyl,        3-pentyl, 2-pentyl, 3-methyl-butyl, 2-propenyl, cyclopropyl,        cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxetanyl,        tetrahydrofuranyl, tetrahydropyranyl, azetidyl, pyrrolidyl,        piperidyl, hexahydroazepinyl, thiolanyl, tetrahydrothiopyranyl,        thiepanyl, 1,4-oxathianyl, 1,3-dioxolanyl, 1,2-dithiolanyl,        1,3-dithiolanyl, hexahydro-pyridazinyl, imidazolidyl,        1,3-dioxanyl, morpholinyl, 1,3-dithianyl, 1,4-dioxanyl,        1,4-dithianyl, or thiomorpholinyl.        Embodiment A104. A compound according to embodiment A103 wherein    -   G¹ is selected from the group consisting of methyl, ethyl,        propyl, butyl, isopropyl, isobutyl, sec-butyl, tert-butyl,        cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,        tetrahydrofuranyl, tetrahydropyranyl, pyrrolidyl, piperidyl,        hexahydroazepinyl, thiolanyl, tetrahydrothiopyranyl, or        thiepanyl.        Embodiment A105. A compound according to embodiment A104 wherein    -   G¹ is selected from the group consisting of methyl, ethyl,        propyl, butyl, isopropyl, isobutyl, cyclopentyl, cyclohexyl,        tetrahydrofuranyl, tetrahydropyranyl, piperidyl, or        hexahydroazepinyl.        Embodiment A106. A compound according to embodiment A105 wherein    -   G¹ is selected from the group consisting of isobutyl,        cyclopentyl, and piperidyl.        Embodiment A107. A compound according to embodiment A105 wherein    -   G¹ is isobutyl.        Embodiment A108. A compound according to embodiment A105 wherein    -   G¹ is cyclopentyl.        Embodiment A109. A compound according to embodiment A105 wherein    -   G¹ is piperidyl.        Embodiment A110. A compound according to any one of the        embodiments A99 to A102, wherein    -   R¹⁸ and R¹⁹, independently of each other, are hydrogen,        C₁₋₆-alkyl, heteroaryl-C₁₋₆-alkylene-, aryl-C₁₋₆-alkylene-,        C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-, heteroaryl, or        aryl.        Embodiment A111. A compound according to embodiment A110,        wherein    -   R¹⁸ and R¹⁹, independently of each other, are hydrogen,        C₁₋₆-alkyl, C₃₋₁₀-heteroaryl-C₁₋₆-alkylene-,        C₃₋₁₀-aryl-C₁₋₆-alkylene-, C₁₋₆-alkyl-C₃₋₁₀-arylene-,        C₁₋₆-alkyl-C₃₋₁₀-heteroarylene-, C₃₋₁₀-heteroaryl, or        C₃₋₁₀-aryl.        Embodiment A112. A compound according to embodiment A111,        wherein    -   R¹⁸ and R¹⁹, independently of each other, are hydrogen or        C₁₋₆-alkyl.        Embodiment A113. A compound according to embodiment A112,        wherein    -   R¹⁸ is hydrogen.        Embodiment A114. A compound according to embodiment A112 or        A113, wherein    -   R¹⁹ is hydrogen.        Embodiment A115. A compound according to embodiment A100 or        embodiment A102, wherein    -   R¹⁸ and R¹⁹, when attached to the same nitrogen atom, together        with the said nitrogen atom forms a 3 to 8 membered heterocyclic        ring optionally containing one or two further heteroatoms        selected from nitrogen, oxygen and sulfur, and optionally        containing one or two double bonds.        Embodiment A116. A compound according to any one of the        embodiments A1 to A98, wherein    -   G¹ is alkyl or cycloalkyl, optionally substituted with one or        more substituents selected from the group consisting of —CN,        —CF₃, —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹ and C₁₋₆-alkyl,    -   or G¹ is aryl optionally substituted with one or more        substituents R⁴⁰, R⁴¹, and R⁴², wherein R¹⁸, R¹⁹, R⁴⁰, R⁴¹, and        R⁴² are as defined in embodiment A1.        Embodiment A117. A compound according to embodiment A116,        wherein    -   G¹ is C₁₋₆-alkyl or C₃₋₁₀-cycloalkyl, optionally substituted        with one or more substituents selected from the group consisting        of —CN, —CF₃, —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹ and C₁₋₆-alkyl,    -   or G¹ is C₃₋₁₀-aryl optionally substituted with one or more        substituents R⁴⁰, R⁴¹, and R⁴², wherein R¹⁸, R¹⁹, R⁴⁰, R⁴¹, and        R⁴² are as defined in embodiment A1.        Embodiment A118. A compound according to embodiment A117,        wherein    -   G¹ is C₁₋₆-alkyl or C₃₋₁₀-cycloalkyl, optionally substituted        with one or more substituents selected from the group consisting        of —CN, —CF₃, —OCF₃, —OR¹⁸, —NR¹⁸R¹⁹ and C₁₋₆-alkyl,    -   or G¹ is phenyl optionally substituted with one or more        substituents R⁴⁰, R⁴¹, and R⁴², wherein R¹⁸, R¹⁹, R⁴⁰, R⁴¹, and        R⁴² are as defined in embodiment A1.        Embodiment A119. A compound according to embodiment A116, A117,        or A118, wherein    -   R¹⁸ and R¹⁹, independently of each other, are hydrogen,        C₁₋₆-alkyl, heteroaryl-C₁₋₆-alkylene-, aryl-C₁₋₆-alkylene-,        C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-, heteroaryl, or        aryl.        Embodiment A120. A compound according to embodiment A119,        wherein    -   R¹⁸ and R¹⁹, independently of each other, are hydrogen,        C₁₋₆-alkyl, C₃₋₁₀-heteroaryl-C₁₋₆-alkylene-,        C₃₋₁₀-aryl-C₁₋₆-alkylene-, C₁₋₆-alkyl-C₃₋₁₀-arylene-,        C₁₋₆-alkyl-C₃₋₁₀-heteroarylene-, C₃₋₁₀-heteroaryl, or        C₃₋₁₀-aryl.        Embodiment A121. A compound according to embodiment A120,        wherein    -   R¹⁸ and R¹⁹, independently of each other, are hydrogen or        C₁₋₆-alkyl.        Embodiment A122. A compound according to embodiment A121,        wherein    -   R¹⁸ is hydrogen.        Embodiment A123. A compound according to embodiment A121 or        A122, wherein    -   R¹⁹ is hydrogen.        Embodiment A124. A compound according to embodiment A116 or        embodiment A117, wherein    -   R¹⁸ and R¹⁹, when attached to the same nitrogen atom, together        with the said nitrogen atom forms a 3 to 8 membered heterocyclic        ring optionally containing one or two further heteroatoms        selected from nitrogen, oxygen and sulfur, and optionally        containing one or two double bonds.        Embodiment A125. A compound according to any one of the        embodiments A116 to A124, wherein    -   R⁴⁰, R⁴¹, and R⁴² independently of each other are    -   halogen, —CN, —NO₂, C₁₋₆-alkyl, —CHF₂, —CF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵,        —SR⁵⁴, —NR⁵⁴S(O)₂R⁵⁵, —S(O)₂NR⁵⁴R⁵⁵, —S(O)NR⁵⁴R⁵⁵, —S(O)R⁵⁴,        —S(O)₂R⁵⁴, —C(O)NR⁵⁴R⁵⁵, —OC(O)NR⁵⁴R⁵⁵, —NR⁵⁴C(O)R⁵⁵,        —CH₂C(O)NR⁵⁴R⁵⁵, —CH₂C(O)OR⁵⁴, —OCH₂C(O)NR⁵⁴R⁵⁵, —CH₂OR⁵⁴,        —CH₂NR⁵⁴R⁵⁵, and —C(O)OR⁵⁴; or    -   C₂₋₆-alkenyl and C₂₋₆-alkynyl, which may optionally be        substituted with one or more substituents selected from —CN,        —CF₃, —OCF₃, —R⁵⁴, —NR⁵⁴R⁵⁵ and C₁₋₆-alkyl, wherein        -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen,            C₁₋₆-alkyl, C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,            aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-, heteroaryl,            or aryl;        -   or        -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom,            together with the said nitrogen atom may form a 3 to 8            membered heterocyclic ring optionally containing one or two            further heteroatoms selected from nitrogen, oxygen and            sulfur, and optionally containing one or two double bonds.            Embodiment A126. A compound according to embodiment A125,            wherein.    -   R⁴⁰, R⁴¹, and R⁴² independently of each other are    -   halogen, —CN, C₁₋₆-alkyl, —CF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵, —SR⁵⁴,        —NR⁵⁴S(O)₂R⁵⁵, —S(O)R⁵⁴, —S(O)₂R⁵⁴, —CH₂C(O)OR⁵⁴, —CH₂OR⁵⁴,        —CH₂NR⁵⁴R⁵⁵, and —C(O)OR⁵⁴; wherein        -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen,            C₁₋₆-alkyl, C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,            aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-, heteroaryl,            or aryl;        -   or        -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom,            together with the said nitrogen atom may form a 3 to 8            membered heterocyclic ring optionally containing one or two            further heteroatoms selected from nitrogen, oxygen and            sulfur, and optionally containing one or two double bonds.            Embodiment A127. A compound according to embodiment A126            wherein    -   R⁴⁰, R⁴¹, and R⁴² independently of each other are    -   halogen, or —OR⁵⁴    -   wherein        -   R⁵⁴ is hydrogen, C₁₋₆-alkyl, C₁₋₆-alkyl-arylene-,            C₁₋₆-alkyl-heteroarylene-, aryl-C₁₋₆-alkylene-,            heteroaryl-C₁₋₆-alkylene-, heteroaryl, or aryl.            Embodiment A128. A compound according to embodiment A126,            wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen, or        C₁₋₆-alkyl, C₁₋₆-alkyl-C₃₋₁₀-arylene-,        C₁₋₆-alkyl-C₃₋₁₀-heteroarylene-, C₃₋₁₀-aryl-C₁₋₆-alkylene-,        C₃₋₁₀-heteroaryl-C₁₋₆-alkylene-, C₃₋₁₀-heteroaryl, or        C₃₋₁₀-aryl.        Embodiment A129. A compound according to embodiment A128,        wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment A130. A compound according to embodiment A129,        wherein    -   R⁵⁴ is hydrogen.        Embodiment A131. A compound according to embodiment A129 or        embodiment A130, wherein    -   R⁵⁵ is hydrogen.        Embodiment A132. A compound according to embodiment A127 wherein    -   R⁵⁴ is methyl.        Embodiment A133. A compound according to any one of the        embodiments A1 to A98, wherein    -   G¹ is aryl or heteroaryl, optionally substituted with one or        more substituents R⁴⁰, R⁴¹, and R⁴², wherein        -   R⁴⁰, R⁴¹, and R⁴² are as defined in embodiment A1.            Embodiment A134. A compound according to embodiment A133,            wherein    -   G¹ is C₃₋₁₀-aryl or C₃₋₁₀-heteroaryl, optionally substituted        with one or more substituents R⁴⁰, R⁴¹, and R⁴², wherein        -   R⁴⁰, R⁴¹, and R⁴² are as defined in embodiment A1.            Embodiment A135. A compound according to embodiment A133,            wherein    -   G¹ is aryl, optionally substituted with one or more substituents        R⁴⁰, R⁴¹, and R⁴², wherein        -   R⁴⁰, R⁴¹, and R⁴² are as defined in embodiment A1.            Embodiment A136. A compound according to embodiment A135,            wherein    -   G¹ is C₃₋₁₀-aryl, optionally substituted with one or more        substituents R⁴⁰, R⁴¹, and R⁴², wherein        -   R⁴⁰, R⁴¹, and R⁴² are as defined in embodiment A1.            Embodiment A137. A compound according to embodiment A136,            wherein    -   G¹ is phenyl, optionally substituted with one or more        substituents R⁴⁰, R⁴¹, and R⁴², wherein        -   R⁴⁰, R⁴¹, and R⁴² are as defined in embodiment A1.            Embodiment A138. A compound according to any one of the            embodiments A133 to A137, wherein    -   R⁴⁰, R⁴¹, and R⁴² independently of each other are    -   halogen, —CN, —NO₂, C₁₋₆-alkyl, —CHF₂, —CF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵,        —SR⁵⁴, —NR⁵⁴S(O)₂R⁵⁵, —S(O)₂NR⁵⁴R⁵⁵, —S(O)NR⁵⁴R⁵⁵, —S(O)R⁵⁴,        —S(O)₂R⁵⁴, —C(O)NR⁵⁴R⁵⁵, —OC(O)NR⁵⁴R⁵⁵, —NR⁵⁴C(O)R⁵⁵,        —CH₂C(O)NR⁵⁴R⁵⁵, —CH₂C(O)OR⁵⁴, —OCH₂C(O)NR⁵⁴R⁵⁵, —CH₂OR⁵⁴,        —CH₂NR⁵⁴R⁵⁵, and —C(O)OR⁵⁴; or    -   C₂₋₆-alkenyl and C₂₋₆-alkynyl, which may optionally be        substituted with one or more substituents selected from —CN,        —CF₃, —OCF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵ and C₁₋₆-alkyl, wherein        -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen,            C₁₋₆-alkyl, C₁₋₅-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,            aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-, heteroaryl,            or aryl;        -   or        -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom,            together with the said nitrogen atom may form a 3 to 8            membered heterocyclic ring optionally containing one or two            further heteroatoms selected from nitrogen, oxygen and            sulfur, and optionally containing one or two double bonds.            Embodiment A139. A compound according to embodiment A138,            wherein    -   R⁴⁰, R⁴¹, and R⁴² independently of each other are    -   halogen, —CN, C₁₋₆-alkyl, —CF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵, —SR⁵⁴,        —NR⁵⁴S(O)₂R⁵⁵, —S(O)R⁵⁴, —S(O)₂R⁵⁴, —CH₂C(O)OR⁵⁴, —CH₂OR⁵⁴,        —CH₂NR⁵⁴R⁵⁵, and —C(O)OR⁵⁴; wherein        -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen,            C₁₋₆-alkyl, C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,            aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-, heteroaryl,            or aryl;        -   or        -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom,            together with the said nitrogen atom may form a 3 to 8            membered heterocyclic ring optionally containing one or two            further heteroatoms selected from nitrogen, oxygen and            sulfur, and optionally containing one or two double bonds.            Embodiment A140. A compound according to embodiment A139            wherein    -   R⁴⁰, R⁴¹, and R⁴² independently of each other are    -   halogen, or —OR⁵⁴    -   wherein    -   R⁵⁴ is hydrogen, C₁₋₆-alkyl, C₁₋₆-alkyl-arylene-,        C₁₋₆-alkyl-heteroarylene-, aryl-C₁₋₆-alkylene-,        heteroaryl-C₁₋₆-alkylene-, heteroaryl, or aryl.        Embodiment A141. A compound according to any one of the        embodiments A138 to A139, wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen, or        C₁₋₆-alkyl, C₁₋₆-alkyl-C₃₋₁₀-arylene-,        C₁₋₆-alkyl-C₃₋₁₀-heteroarylene-, C₃₋₁₀-aryl-C₁₋₆-alkylene-,        C₃₋₁₀-heteroaryl-C₁₋₆-alkylene-, C₃₋₁₀-heteroaryl, or        C₃₋₁₀-aryl.        Embodiment A142. A compound according to embodiment A141,        wherein    -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment A143. A compound according to embodiment A142,        wherein    -   R⁵⁴ is hydrogen.        Embodiment A144. A compound according to embodiment A142 or        embodiment A143, wherein    -   R⁵⁵ is hydrogen.        Embodiment A145. A compound according to embodiment A140 wherein    -   R⁵⁴ is methyl.        Embodiment A146. A compound according to embodiment A135,        wherein        G¹ is        R⁵⁶, R⁵⁷, R⁵⁸, R⁵⁹, and R⁶⁰, independently of each other, are        hydrogen or halogen, —CN, —NO₂, C₁₋₆-alkyl, —CHF₂, —CF₃, —OCF₃,        —OCHF₂, —OCH₂CF₃, —OCF₂CHF₂, —S(O)₂CF₃, —SCF₃, —OR⁶¹, —NR⁶¹R⁶²,        —SR⁶¹, —NR⁶¹S(O)₂R⁶², —S(O)₂NR⁶¹R⁶², —S(O)NR⁶¹R⁶², —S(O)R⁶¹,        —S(O)₂R⁶¹, —C(O)NR⁶¹R⁶², —OC(O)NR⁶¹R⁶², —NR⁶¹C(O)R⁶²,        —CH₂C(O)NR⁶¹R⁶², —CH₂C(O)OR⁶¹, —OCH₂C(O)NR⁶¹R⁶², —CH₂OR⁶¹,        —CH₂NR⁶¹R⁶², —OC(O)R⁶¹, —C(O)R⁶¹ and —C(O)OR⁶¹; or        C₂₋₆-alkenyl and C₂₋₆-alkynyl, which may optionally be        substituted with one or more substituents selected from —CN,        —CF₃, —OCF₃, —OR⁶¹, —NR⁶¹R⁶² and C₁₋₆-alkyl; C₃₋₁₀-cycloalkyl,        C₄₋₈-cycloalkenyl, heterocyclyl,        C₃₋₁₀-cycloalkyl-C₁₋₆-alkylene-, C₃₋₁₀-cyclo-alkyl-C₁₋₆-alkoxy-,        C₃₋₁₀-cycloalkyloxy, C₃₋₁₀-cycloalkyl-C₁₋₆-alkylthio-,        C₃₋₁₀-cycloalkylthio, C₃₋₁₀-cycloalkyl-C₂₋₆-alkenylene-,        C₃₋₁₀-cycloalkyl-C₂₋₆-alkynylene-,        C₄₋₈-cycloalkenyl-C₁₋₆-alkylene-,        C₄₋₈-cycloalkenyl-C₂₋₆-alkenylene-,        C₄₋₈-cycloalkenyl-C₂₋₆-alkynylene-, heterocyclyl-C₁₋₆-alkylene-,        heterocyclyl-C₂₋₆-alkenylene-, heterocyclyl-C₂₋₆-alkynylene-; or        aryl, aryloxy, aryloxycarbonyl, aroyl, aryl-C₁₋₆-alkoxy-,        aryl-C₁₋₆-alkylene-, aryl-C₂₋₆-alkenylene-,        aryl-C₂₋₆-alkynylene-, heteroaryl, heteroaryl-C₁₋₆-alkylene-,        heteroaryl-C₂₋₆-alkenylene- and heteroaryl-C₂₋₆-alkynylene-, of        which the aryl and heteroaryl moieties optionally may be        substituted with one or more substituents selected from halogen,        —C(O)OR⁶¹, —CN, —CF₃, —OCF₃, —NO₂, —OR⁶¹, —NR⁶¹R⁶² or        C₁₋₆-alkyl, wherein    -   R⁶¹ and R⁶² independently of each other are hydrogen,        C₁₋₆-alkyl, C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,        aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-, heteroaryl, or        aryl;    -   or    -   R⁶¹ and R⁶², when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds.        Embodiment A147. A compound according to embodiment A146,        wherein    -   R⁵⁶, R⁵⁷, R⁵⁸, R⁵⁹, and R⁶⁰ independently of each other are    -   halogen, —CN, —NO₂, C₁₋₆-alkyl, —CHF₂, —CF₃, —OR⁶¹, —NR⁶¹R⁶²,        —SR⁶¹, —NR⁶¹S(O)₂R⁶², —S(O)₂NR⁶¹R⁶², —S(O)NR⁶¹R⁶², —S(O)R⁶¹,        —S(O)₂R⁶¹, —C(O)NR⁶¹R⁶², —OC(O)NR⁶¹R⁶², —NR⁶¹C(O)R⁶²,        —CH₂C(O)NR⁶¹R⁶², —CH₂C(O)OR⁶¹, —OCH₂C(O)NR⁶¹R⁶², —CH₂OR⁶¹,        —CH₂NR⁶¹R⁶², and —C(O)OR⁶¹; or    -   C₂₋₆-alkenyl and C₂₋₆-alkynyl, which may optionally be        substituted with one or more substituents selected from —CN,        —CF₃, —OCF₃, —OR⁶¹, —NR⁶¹R⁶² and C₁₋₆-alkyl, wherein        -   R⁶¹ and R⁶² independently of each other are hydrogen,            C₁₋₆-alkyl, C₁₋₆-alkyl-arylene-, C₁₋₆-alkyl-heteroarylene-,            aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-, heteroaryl,            or aryl;        -   or        -   R⁶¹ and R⁶², when attached to the same nitrogen atom,            together with the said nitrogen atom may form a 3 to 8            membered heterocyclic ring optionally containing one or two            further heteroatoms selected from nitrogen, oxygen and            sulfur, and optionally containing one or two double bonds.            Embodiment A148. A compound according to embodiment A146 or            embodiment A147, wherein R⁵⁶ or R⁵⁷ is —OR⁶¹.            Embodiment A149. A compound according to embodiment A148            wherein R⁶¹ is methyl.            Embodiment A150. A compound according to embodiment A147,            wherein    -   R⁶¹ and R⁶² independently of each other are hydrogen, or        C₁₋₆-alkyl, C₁₋₆-alkyl-C₃₋₁₀-arylene-,        C₁₋₆-alkyl-C₃₋₁₀-heteroarylene-, C₃₋₁₀-aryl-C₁₋₆-alkylene-,        C₃₋₁₀-heteroaryl-C₁₋₆-alkylene-, C₃₋₁₀-heteroaryl, or        C₃₋₁₀-aryl.        Embodiment A151. A compound according to embodiment A150,        wherein    -   R⁶¹ and R⁶² independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment A152. A compound according to embodiment A151,        wherein    -   R⁶¹ is hydrogen.        Embodiment A153. A compound according to embodiment A151 or        embodiment A152, wherein    -   R⁶² is hydrogen.        Embodiment A154. A compound according to any one of the        embodiments A146 to A153, wherein    -   at least one of R⁵⁶, R⁵⁷, R⁵⁸, R⁵⁹, and R⁶⁰ are hydrogen.        Embodiment A155. A compound according to embodiment A154,        wherein    -   at least two of R²³, R²⁴, R²⁵, and R²⁶ are hydrogen.        Embodiment A156. A compound according to embodiment A155,        wherein    -   at least three of R²³, R²⁴, R²⁵, and R²⁶ are hydrogen.        Embodiment A157. A compound according to any one of the        embodiments A1 to A156, wherein    -   L² is a direct bond, C₁₋₆-alkylene, C₂₋₆-alkenylene,        C₂₋₆-alkynylene, —N—R²⁰—, —C₁₋₆-alkylene-N(R²⁰)—,        —C₂₋₆-alkenylene-N(R²⁰)—, or —C₂₋₆-alkynylene-N(R²⁰)—, wherein        -   R²⁰ is as defined in embodiment A1.            Embodiment A158. A compound according to any one of the            embodiments A1 to A153, wherein    -   L² is —N—R²⁰—, -alkylene-N(R²⁰)—, -alkenylene-N(R²⁰)—, or        -alkynylene-N(R²⁰)—, wherein        -   R²⁰ is as defined in embodiment A1.            Embodiment A159. A compound according to embodiment A157 or            embodiment A158, wherein    -   L² is —N—R²⁰—, —C₁₋₆-alkylene-N(R²⁰)—, —C₂₋₆-alkenylene-N(R²⁰)—,        or —C₂₋₆-alkynylene-N(R²⁰)—, wherein        -   R²⁰ is as defined in embodiment A1.            Embodiment A160. A compound according to embodiment A159,            wherein    -   L² is —NR²⁰, wherein        -   R²⁰ is as defined in embodiment A1.            Embodiment A161. A compound according to embodiment A157,            wherein    -   L² is a direct bond.        Embodiment A162. A compound according to any one of the        embodiments A1 to A160, wherein    -   R²⁰ is hydrogen, or    -   R²⁰ is C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl,        C₃₋₁₀-cycloalkyl-W³—, C₃₋₁₀-heterocyclyl-W³—, C₃₋₁₀-aryl-W³—, or        C₄₋₁₀-heteroaryl-W³—, optionally substituted with one or more        substituents R³⁰, R³¹, and R³² wherein        -   W³, R³⁰, R³¹, and R³² are as defined in embodiment A1.            Embodiment A163. A compound according to embodiment A162,            wherein    -   W³ is alkylene.        Embodiment A164. A compound according to embodiment A163,        wherein    -   W³ is C₂₋₆-alkylene.        Embodiment A165. A compound according to embodiment A162,        wherein    -   W³ is a direct bond.        Embodiment A166. A compound according to any one of the        embodiments A1 to A160, wherein    -   R²⁰ is hydrogen, C₁₋₆-alkyl, C₂₋₆-alkenyl, or C₂₋₆-alkynyl,        optionally substituted with one or more substituents R³⁰, R³¹,        and R³² wherein        -   R³⁰, R³¹, and R³² are as defined in embodiment A1.            Embodiment A167. A compound according to any one of the            embodiments A162 to A166, wherein    -   R²⁰ is hydrogen, or    -   R²⁰ is C₁₋₆-alkyl, C₁₋₆-alkenyl, or C₁₋₆-alkynyl, optionally        substituted with one or more substituents R³⁰, R³¹, and R³²,        wherein        -   R³⁰, R³¹, and R³² are as defined in embodiment A1.            Embodiment A168. A compound according to any one of the            embodiments A1 to A167, wherein    -   R³⁰, R³¹, and R³² independently of each other are selected from        —CHF₂, —CF₃, —OCF₃, —OCHF₂, —OCH₂CF₃, —OCF₂CHF₂, —S(O)₂CF₃,        —SCF₃, —OR⁵², —NR⁵²R⁵³, —SR₅₂, —NR⁵²S(O)₂R⁵³, —S(O)₂NR⁵²R⁵³,        —S(O)NR⁵²R⁵³, —S(O)R⁵², —S(O)₂R⁵², —C(O)NR⁵²R⁵³, —OC(O)NR⁵²R⁵³,        —NR⁵²C(O)R⁵³, —CH₂C(O)NR⁵²R⁵³, —OCH₂C(O)NR⁵²R⁵³, —CH₂OR⁵²,        —CH₂NR⁵²R⁵³, —OC(O)R⁵², —C(O)R⁵² and —C(O)OR⁵², wherein        -   R⁵² and R⁵³ are as defined in embodiment A1.            Embodiment A169. A compound according to embodiment A168,            wherein    -   R⁵² and R⁵³, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds.        Embodiment A170. A compound according to any one of the        embodiments A1 to A168, wherein    -   R⁵² and R⁵³ independently of each other are hydrogen,        C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene-heteroaryl-C₁₋₆-alkylene-heteroaryl, or aryl.        Embodiment A171. A compound according to embodiment A170,        wherein    -   R⁵² and R⁵³ independently of each other are hydrogen,        C₁₋₆-alkyl, aryl-C₁₋₆-alkylene- or aryl.        Embodiment A172. A compound according to embodiment A171,        wherein    -   R⁵² and R⁵³ independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment A173. A compound according to embodiment A172,        wherein    -   R⁵² is hydrogen.        Embodiment A174. A compound according to embodiment A172 or        embodiment A173, wherein    -   R⁵³ is hydrogen.        Embodiment A175. A compound according to embodiment A167,        wherein    -   R²⁰ is hydrogen.        Embodiment A176. A compound according to any one of the        embodiments A1 to A175, wherein    -   L³ is —C(O)—, —C(O)—C(O)— or —C(O)CH₂C(O)—.        Embodiment A177. A compound according to embodiment A176 wherein    -   L³ is —C(O)—.        Embodiment A178. A compound according to embodiment A176 wherein        L³ is —C(O)—C(O)—.        Embodiment A179. A compound according to embodiment A176 wherein        L³ is —C(O)CH₂C(O)—.        Embodiment A180. A compound according to any one of the        embodiments A1 to A179, wherein    -   R¹ is hydrogen, or    -   R¹ is C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl,        C₃₋₁₀-cycloalkyl-W⁴—, C₃₋₁₀-heterocyclyl-W⁴—, C₃₋₁₀-aryl-W⁴—, or        C₄₋₁₀-heteroaryl-W⁴—, optionally substituted with one or more        substituents R³³, R³⁴, and R³⁵ wherein        -   W⁴, R³³, R³⁴, and R³⁵ are as defined in embodiment A1.            Embodiment A181. A compound according to embodiment A180,            wherein    -   W⁴ is alkylene.        Embodiment A182. A compound according to embodiment A181,        wherein    -   W⁴ is C₂₋₆-alkylene.        Embodiment A183. A compound according to embodiment A180,        wherein    -   W⁴ is a direct bond.        Embodiment A184. A compound according to any one of the        embodiments A1 to A176, wherein    -   R¹ is hydrogen, C₁₋₆-alkyl, C₂₋₆-alkenyl, or C₂₋₆-alkynyl,        optionally substituted with one or more substituents R³³, R³⁴,        and R³⁵, wherein        -   R³³, R³⁴, and R³⁵ are as defined in embodiment A1.            Embodiment A185. A compound according to any one of the            embodiments A180 to A184, wherein    -   R¹ is hydrogen, C₁₋₆-alkyl, C₂₋₆-alkenyl, or C₂₋₆-alkynyl,        optionally substituted with one or more substituents R³³, R³⁴,        and R³⁵, wherein        -   R³³, R³⁴, and R³⁵ are as defined in embodiment A1.            Embodiment A186. A compound according to embodiment A185,            wherein    -   R¹ is hydrogen or C₁₋₆-alkyl optionally substituted with one or        more substituents R³³, R³⁴ and R³⁵ wherein        -   R³³, R³⁴, and R³⁵ are as defined in embodiment A1.            Embodiment A187. A compound according to any one of the            embodiments A1 to A186, wherein    -   R³³, R³⁴, and R³⁵ independently of each other are selected from        —CHF₂, —CF₃, —OCF₃, —OCHF₂, —OCH₂CF₃, —OCF₂CHF₂, —S(O)₂CF₃,        —SCF₃, —OR⁵², —NR⁵²R⁵³, —SR₅₂, —NR⁵²S(O)₂R⁵³, —S(O)₂NR⁵²R⁵³,        —S(O)NR⁵²R⁵³, —S(O)R⁵², —S(O)₂R⁵², —C(O)NR⁵²R⁵³, —OC(O)NR⁵²R⁵³,        —NR⁵²C(O)R⁵³, —CH₂C(O)NR⁵²R⁵³, —OCH₂C(O)NR⁵²R⁵³, —CH₂OR⁵²,        —CH₂NR⁵²R⁵³, —OC(O)R⁵², —C(O)R⁵² and —C(O)OR⁵², wherein        -   R⁵² and R⁵³ are as defined in embodiment A1.            Embodiment A188. A compound according to embodiment A186,            wherein    -   R⁵² and R⁵³, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds.        Embodiment A189. A compound according to embodiment A186,        wherein    -   R⁵² and R⁵³ independently of each other are hydrogen,        C₁₋₆-alkyl,        aryl-C₁₋₆-alkylene-heteroaryl-C₁₋₆-alkylene-heteroaryl, or aryl.        Embodiment A190. A compound according to embodiment A189,        wherein    -   R⁵² and R⁵³, independently of each other are hydrogen,        C₁₋₆-alkyl, aryl-C₁₋₆-alkylene- or aryl.        Embodiment A191. A compound according to embodiment A190,        wherein    -   R⁵² and R⁵³ independently of each other are hydrogen or        C₁₋₆-alkyl.        Embodiment A192. A compound according to embodiment A191,        wherein    -   R⁵² is hydrogen.        Embodiment A193. A compound according to embodiment A191 or        embodiment A192, wherein    -   R⁵³ is hydrogen.        Embodiment A194. A compound according to embodiment A186,        wherein    -   R¹ is hydrogen.        Embodiment A195. A compound according to any one of the        embodiments A1 to A194, wherein    -   G² is heteroaryl, fused heterocyclylheteroaryl, or fused        cycloalkylheteroaryl, optionally substituted with one or more        substituents R⁴³, R⁴⁴, and R⁴⁵, wherein said heteroaryl group        possesses a nitrogen atom adjacent to the atom joining G² with        —N(R)—, and wherein        -   R⁴³, R⁴⁴, and R⁴⁵ are as defined in embodiment A1.            Embodiment A196. A compound according to embodiment A195,            wherein    -   G² is fused cycloalkylheteroaryl optionally substituted with one        or more substituents R⁴³, R⁴⁴, and R⁴⁵, wherein said heteroaryl        group possesses a nitrogen atom adjacent to the atom joining G²        with —N(R)—, and wherein        -   R⁴³, R⁴⁴, and R⁴⁵ are as defined in embodiment A1.            Embodiment A197. A compound according to embodiment A196            wherein    -   G² is fused cycloalkylthiazolyl optionally substituted with one        or more substituents R⁴³, R⁴⁴, and R⁴⁵ and wherein        -   R⁴³, R⁴⁴, and R⁴⁵ are as defined in embodiment A1.            Embodiment A198. A compound according to embodiment A197,            wherein    -   G² is fused cycloalkylthiazolyl optionally substituted with        —COOH        Embodiment A199. A compound according to embodiment A195,        wherein    -   G² is heteroaryl optionally substituted with one or more        substituents R⁴³, R⁴⁴, and R⁴⁵, wherein said heteroaryl group        possesses a nitrogen atom adjacent to the atom joining G² with        —N(R¹)—, and wherein        -   R⁴³, R⁴⁴, and R⁴⁵ are as defined in embodiment A1.            Embodiment A200. A compound according to embodiment A199,            wherein    -   G² is furanyl, thienyl, thiophenyl, pyrrolyl, imidazolyl,        pyrazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl,        isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridinyl,        pyridazinyl, pyrazinyl, pyrimidinyl, quinolinyl, isoquinolinyl,        benzofuranyl, benzothiophenyl, indolyl, or indazolyl, optionally        substituted with one or more substituents R⁴³, R⁴⁴, and R⁴⁵,        wherein        -   R⁴³, R⁴⁴, and R⁴⁵ are as defined in embodiment A1.            Embodiment A201. A compound according to embodiment A200            wherein G² is thiazolyl, optionally substituted with one or            more substituents R⁴³, R⁴⁴, and R⁴⁵, wherein    -   R⁴³, R⁴⁴, and R⁴⁵ are as defined in embodiment A1.        Embodiment A202. A compound according to embodiment A201 wherein        G² is    -   wherein    -   R⁴³ and R⁴⁴ are as defined in embodiment A1.        Embodiment A203. A compound according to embodiment A202 wherein        G² is    -   wherein    -   R⁴³ is as defined in embodiment A1.        Embodiment A204. A compound according to embodiment A202 wherein        G² is    -   wherein    -   R⁴³ and R⁴⁴ are as defined in embodiment A1.        Embodiment A205. A compound according to embodiment A200 wherein        G² is    -   wherein        -   R⁴³ is as defined in embodiment A1.            Embodiment A206. A compound according to embodiment A202            wherein G² is            wherein            R⁴⁴ is as defined in embodiment A1.            Embodiment A207. A compound according to any one of the            embodiments A1 to A206, wherein    -   R⁴³, R⁴⁴, and R⁴⁵ independently of each other are selected from    -   —CN, —NO₂, —SCF₃, —OR⁵⁴, —NR⁵⁴R⁵⁵, —SR⁵⁴, —S(O)₂NR⁵⁴R⁵⁵,        —S(O)NR⁵⁴R⁵⁵, —S(O)R⁵⁴, —S(O)₂R⁵⁴, —C(O)NR⁵⁴R⁵⁵, —OC(O)NR⁵⁴R⁵⁵,        —NR⁵⁴C(O)R⁵⁵, halogen, —S—C₁₋₆-alkylene-OR⁵⁴,        —S(O)₂—C₁₋₆-alkylene-OR⁵⁴, —C₁₋₆-alkylene-S—R⁵⁴,        —C₁₋₆-alkylene-S(O)R⁵⁴, —C₁₋₆-alkylene-S(O)₂R⁵⁴,        —C₁₋₆-alkylene-N(R⁵⁴)S(O)₂R⁵⁵, —N(R⁵⁴)S(O)₂R⁵⁵,        —C₁₋₆-alkylene-C(O)NR⁵⁴R⁵⁵, —C₁₋₆-alkylene-N(R⁵⁴)C(O)R⁵⁵,        —N(R⁵⁴)C(O)R⁵⁵, —C₁₋₆-alkylene-N(R⁵⁴)C(O)NR⁵⁵R⁵⁶,        C₁₋₆-alkylene-NHC(═NR⁵⁴)NR⁵⁵R⁵⁶, —C₁₋₆-alkylene-N(R⁵⁴)C(O)OR⁵⁵,        —N(R⁵⁴)C(O)OR⁵⁵, —C₁₋₆-alkylene-C(O)OR⁵⁴, —OCH₂C(O)NR⁵⁴R⁵⁵,        —O(CH₂)₁₋₃OR⁵⁴, —C₁₋₆-alkylene-O—R⁵⁴, —C₁₋₆-alkylene-C(O)R⁵⁴,        —C₁₋₆-alkylene-NR⁵⁴R⁵⁵, —C₁₋₆-alkylene=N—O—R⁵⁴,        —C₁₋₆-alkylene-N(R⁵⁴)S(O)₂NR⁵⁵R⁵⁶, —N(R⁵⁴)S(O)₂NR⁵⁵R⁵⁶,        —N(R)S(O)₂NR⁵⁵R⁵⁶, —OC(O)R⁵⁴, —C(O)N(R⁵⁴)S(O)₂R⁵⁵,        —C₁₋₆-alkylene-C(R⁵⁴)═N—OR⁵⁵, —NHC(═NR⁵⁴)NR⁵⁵R⁵⁶,        —C₁₋₆-alkylene-N═C(N(R⁵⁴R⁵⁵))₂, —N═C(N(R⁵⁴R⁵⁵))₂, —C(O)R⁵⁴ and        —C(O)OR⁵⁴; or    -   C₁₋₆-alkyl or C₂₋₆-alkenyl, each of which may optionally be        substituted with one or more substituents independently selected        from halogen, R⁵⁴, —CN, —CF₃, —OCF₃, —OR⁵⁴, —C(O)OR⁵⁴, —NR⁵⁴R⁵⁵        and C₁₋₆-alkyl; or    -   C₃₋₁₀-cycloalkyl, heterocyclyl, C₃₋₁₀-cycloalkyl-C₁₋₆-alkylene-,        C₃₋₁₀-cycloalkyl-C₁₋₆-alkoxy-, C₃₋₁₀-cycloalkyloxy,        heterocyclyl-C₁₋₆-alkylene-, of which the heterocyclyl moieties        optionally may be substituted with one or more substituents        independently selected from R⁷⁰; or    -   aryl, aryloxy, aryl-C₁₋₆-alkoxy-, aryl-C₁₋₆-alkylene-,        heteroaryl, heteroaryl-C₁₋₆-alkylene-, of which the aryl and        heteroaryl moieties optionally may be substituted with one or        more substituents selected from halogen, —C(O)OR⁵⁴, —CN, —CF₃,        —OCF₃, —NO₂, —OR⁵⁴, —NR⁵⁴R⁵⁵ or C₁₋₆-alkyl, wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ are as defined in embodiment A1.        Embodiment A208. A compound according to embodiment A207,        wherein    -   R⁴³, R⁴⁴, and R⁴⁵ independently of each other are selected from    -   —OR⁵⁴, —NR⁵⁴R⁵⁵, —SR⁵⁴, —S(O)R⁵⁴, —S(O)₂R⁵⁴, —C(O)NR⁵⁴R⁵⁵,        halogen, —S—C₁₋₆-alkylene-OR⁵⁴, —C₁₋₆-alkylene-S—R⁵⁴,        —C₁₋₆-alkylene-S(O)R⁵⁴, —C₁₋₆-alkylene-S(O)₂R⁵⁴,        —C₁₋₆-alkylene-N(R⁵⁴)S(O)₂R⁵⁵, —C₁₋₆-alkylene-C(O)NR⁵⁴R⁵⁵,        —C₁₋₆-alkylene-N(R⁵⁴)C(O)R⁵⁵, —C₁₋₅-alkylene-N(R⁵⁴)C(O)NR⁵⁵R⁵⁶,        C₁₋₆-alkylene-NHC(═NR⁵⁴)NR⁵⁵R⁵⁶, —C₁₋₆-alkylene-N(R⁵⁴)C(O)OR⁵⁵,        —C₁₋₆-alkylene-C(O)OR⁵⁴, —C₁₋₆-alkylene-O—R⁵⁴,        —C₁₋₆-alkylene-C(O)R⁵⁴, —C₁₋₆-alkylene-NR⁵⁴R⁵⁵,        —C₁₋₆-alkylene=N—O—R⁵⁴, —C₁₋₆-alkylene-N═C(N(R⁵⁴R⁵⁵))₂,        —N═C(N(R⁵⁴R⁵⁵))₂, —C(O)R⁵⁴ and —C(O)OR⁵⁴; or    -   C₁₋₆-alkyl optionally substituted with one or more substituents        independently selected from halogen, R⁵⁴, —CN, —CF₃, —OCF₃,        —OR⁵⁴, —C(O)OR⁵⁴, —NR⁵⁴R⁵⁵ and C₁₋₆-alkyl; or    -   Heterocyclyl or heterocyclyl-C₁₋₆-alkylene-, of which the        heterocyclyl moieties optionally may be substituted with one or        more substituents independently selected from R⁷⁰; or    -   aryl, aryl-C₁₋₆-alkylene-, heteroaryl,        heteroaryl-C₁₋₆-alkylene-, of which the aryl and heteroaryl        moieties optionally may be substituted with one or more        substituents selected from halogen, —C(O)OR⁵⁴, —CN, —CF₃, —OCF₃,        —NO₂, —OR⁵⁴, —NR⁵⁴R⁵⁵ or C₁₋₆-alkyl, wherein    -   R⁵⁴, R⁵⁵, R⁵⁶, and R⁷⁰ are as defined in embodiment A1.        Embodiment A209. A compound according to embodiment A208,        wherein    -   R⁴³, R⁴⁴, and R⁴⁵ independently of each other are selected from    -   —SR⁵⁴, —S(O)R⁵⁴, —S(O)₂R⁵⁴; halogen, —C₁₋₆-alkylene-S—R⁵⁴,        —C₁₋₆-alkylene-S(O)R⁵⁴, —C₁₋₆-alkylene-S(O)₂R⁵⁴,        —C₁₋₆-alkylene-N(R⁵⁴)C(O)OR⁵⁵, —C₁₋₆-alkylene-C(O)OR⁵⁴,        —C₁₋₆-alkylene-O—R⁵⁴, —C₁₋₆-alkylene-NR⁵⁴R⁵⁵,        —C₁₋₆-alkylene-C(O)R⁵⁴, —C(O)R⁵⁴ and —C(O)OR⁵⁴; or    -   C₁₋₆-alkyl optionally substituted with one or more substituents        independently selected from halogen, R⁵⁴, —CN, —CF₃, —OCF₃,        —OR⁵⁴, —C(O)OR⁵⁴, —NR⁵⁴R⁵⁵ and C₁₋₆-alkyl; or    -   Heterocyclyl or heterocyclyl-C₁₋₆-alkylene-, of which the        heterocyclyl moieties optionally may be substituted with one or        more substituents independently selected from R⁷⁰; or    -   heteroaryl or heteroaryl-C₁₋₆-alkylene-, of which the aryl and        heteroaryl moieties optionally may be substituted with one or        more substituents selected from halogen, —C(O)OR⁵⁴, —CN, —CF₃,        —OCF₃, —NO₂, —OR⁵⁴, —NR⁵⁴R⁵⁵ or C₁₋₆-alkyl, wherein    -   R⁵⁴, R⁵⁵, R⁵⁶, and R⁷⁰ are as defined in embodiment A1.        Embodiment A210. A compound according to embodiment A209,        wherein    -   R⁴³, R⁴⁴, and R⁴⁵ independently of each other are selected from    -   —SR⁵⁴, —S(O)₂R⁵⁴, halogen, —C₁₋₆-alkylene-C(O)OR⁵⁴, and        —C(O)OR⁵⁴; or    -   Heterocyclyl or heterocyclyl-C₁₋₆-alkylene-, of which the        heterocyclyl moieties optionally may be substituted with one or        more substituents independently selected from R⁷⁰; or    -   heteroaryl or heteroaryl-C₁₋₆-alkylene-, of which the heteroaryl        moieties optionally may be substituted with one or more        substituents selected from halogen, —C(O)OR⁵⁴, —CN, —CF₃, —OCF₃,        —NO₂, —OR⁵⁴R⁵⁵, —NR⁵⁴R⁵⁵ or C₁₋₆-alkyl, wherein    -   R⁵⁴, R⁵⁵, R⁵⁶, and R⁷⁰ are as defined in embodiment A1.        Embodiment A211. A compound according to embodiment A210,        wherein    -   R⁴³, R⁴⁴, and R⁴⁵ independently of each other are selected from    -   —SR⁵⁴, —S(O)₂R⁵⁴, halogen, —C₁₋₆-alkylene-C(O)OR⁵⁴, and        —C(O)OR⁵⁴; or heterocyclyl-C₁₋₆-alkylene-, wherein    -   heterocyclyl is selected from imidazolyl, piperidyl,        piperazinyl, and morpholinyl, and of which the heterocyclyl        moieties optionally may be substituted with one or more        substituents independently selected from R⁷⁰; or    -   heteroaryl or heteroaryl-C₁₋₆-alkylene-, wherein heteroaryl is        selected from thiazolyl, triazolyl, or tetrazolyl, and of which        the heteroaryl moieties optionally may be substituted with one        or more substituents selected from halogen, —C(O)OR⁵⁴, —CN,        —CF₃, —OCF₃, —NO₂, —OR⁵⁴, —NR⁵⁴R⁵⁵ or C₁₋₆-alkyl, wherein    -   R⁵⁴, R⁵⁵, R⁵⁶, and R⁷⁰ are as defined in embodiment A1.        Embodiment A212. A compound according to embodiment A209,        wherein    -   R⁴³, R⁴⁴, and R⁴⁵ independently of each other are selected from    -   —C₁₋₆-alkylene-S—R⁵⁴, —C₁₋₆-alkylene-O—R⁵⁴,        —C₁₋₆-alkylene-S(O)₂R⁵⁴ or —C₁₋₆-alkylene-NR⁵⁴R⁵⁵, wherein    -   R⁵⁴ and R⁵⁵ are as defined in embodiment A1.        Embodiment A213. A compound according to embodiment A209,        wherein    -   R⁴³ is —C₁₋₆-alkylene-S—R⁵⁴, wherein        -   R⁵⁴ is as defined in embodiment A1.            Embodiment A214. R⁴³ is —C₁₋₆-alkylene-O—R⁵⁴, wherein    -   R⁵⁴ is as defined in embodiment A1.        Embodiment A215. R⁴³ is —C₁₋₆-alkylene-NR⁵⁴R⁵⁵, wherein    -   R⁵⁴ and R⁵⁵ are as defined in embodiment A1.        Embodiment A216. R⁴³ is —C₁₋₆-alkylene-S(O)₂R⁵⁴, wherein    -   R⁵⁴ is as defined in embodiment A1.        Embodiment A217. A compound according to any one of the        embodiments A207 to A210 wherein R⁴³ is heteroaryl or        heteroaryl-C₁₋₆-alkylene- optionally substituted with one or        more substituents selected from halogen, —C(O)OR⁵⁴, —CN, —CF₃,        —OCF₃, —NO₂, —OR⁵⁴, —NR⁵⁴R⁵⁵ or C₁₋₆-alkyl, wherein R⁵⁴ and R⁵⁵        are as defined in embodiment A1.        Embodiment A218. A compound according to embodiment A217 wherein        R⁴³ is heteroaryl optionally substituted with one or more        substituents selected from halogen, —C(O)OR⁵⁴, —CN, —CF₃, —OCF₃,        —NO₂, —OR⁵⁴, —NR⁵⁴R⁵⁵ or C₁₋₆-alkyl, wherein R⁵⁴ and R⁵⁵ are as        defined in embodiment A1.        Embodiment A219. A compound according to embodiment A217 wherein        R⁴³ is heteroaryl-C₁₋₆-alkylene- optionally substituted with one        or more substituents selected from halogen, —C(O)OR⁵⁴, —CN,        —CF₃, —OCF₃, —NO₂, —OR⁵⁴, —NR⁵⁴R⁵⁵ or C₁₋₆-alkyl, wherein R⁵⁴        and R⁵⁵ are as defined in embodiment A1.        Embodiment A220. A compound according to any one of the        embodiments A207 to A211 wherein R⁷⁰ is ═O, methyl or C(O)OR⁷⁵.        Embodiment A221. A compound according to any one of the        embodiments A207 to A211 wherein R⁷⁰ is —C(O)OH        Embodiment A222. A compound according to any one of the        embodiments A207 to A211 wherein R⁷⁰ is —(CH₂)₁₋₃C(O)OH.        Embodiment A223. A compound according to any one of the        embodiments A207 to A211 wherein R⁷⁰ is —S(O)₂CH₃.        Embodiment A224. A compound according to embodiment A211 wherein        R⁴³ is —C₁₋₆-alkylene-C(O)OR⁵⁴.        Embodiment A225. A compound according to embodiment A224 wherein        R⁴³ is —CH₂—C(O)OR⁵⁴.        Embodiment A226. A compound according to embodiment A211 wherein        R⁴⁴ is —SR⁵⁴.        Embodiment A227. A compound according to embodiment A211 wherein        R⁴⁴ is —S(O)₂R⁵⁴.        Embodiment A228. A compound according to embodiment A211 wherein        R⁴⁴ is halogen.        Embodiment A229. A compound according to any one of the        embodiments A1 to A228 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are hydrogen,        C₁₋₆-alkyl, aryl-C₁₋₆-alkylene-, heteroaryl-C₁₋₆-alkylene-,        heterocyclyl, heterocyclyl-C₁₋₆-alkylene-, heteroaryl, or aryl,        each of which is optionally substituted with one or more        substituents independently selected from R⁷¹;    -   or        -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen or            —(CHR⁷²)_(u)—(CHR⁷³)_(v)—W⁶,    -   or    -   R⁵⁴ and R⁵⁵, when attached to the same nitrogen atom, together        with the said nitrogen atom may form a 3 to 8 membered        heterocyclic ring optionally containing one or two further        heteroatoms selected from nitrogen, oxygen and sulfur, and        optionally containing one or two double bonds, and optionally        substituted with one or more C₁₋₆-alkyl groups,    -   wherein R⁷¹, R⁷², R⁷³, u, v, and W⁶ are as defined in embodiment        A1.        Embodiment A230. A compound according to embodiment A229 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are hydrogen,        C₁₋₆-alkyl, heterocyclyl, heterocyclyl-C₁₋₆-alkylene-,        heteroaryl, or aryl, each of which is optionally substituted        with one or more substituents independently selected from R⁷¹;    -   or        -   R⁵⁴ and R⁵⁵ independently of each other are hydrogen or            —(CHR⁷²)_(u)—(CHR⁷³)_(v)—W⁶,    -   wherein R⁷¹, R⁷², R⁷³, u, v, and W⁶ are as defined in embodiment        A1.        Embodiment A231. A compound according to any one of the        embodiments A1 to A230 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are hydrogen,        methyl, ethyl, propyl, butyl, isopropyl, isobutyl, sec-butyl,        tert-butyl, 3-pentyl, 2-pentyl, or 3-methyl-butyl.        Embodiment A232. A compound according to embodiment A231 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are hydrogen,        methyl, ethyl, propyl, butyl, isopropyl, isobutyl, sec-butyl, or        tert-butyl.        Embodiment A233. A compound according to embodiment A232 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are hydrogen,        methyl, ethyl, propyl, butyl, isopropyl, isobutyl, sec-butyl, or        tert-butyl.        Embodiment A234. A compound according to embodiment A233 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are hydrogen,        methyl or ethyl.        Embodiment A235. A compound according to embodiment A234 wherein    -   R⁵⁴ is hydrogen.        Embodiment A236. A compound according to any one of the        embodiments A1 to A230 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are oxetanyl,        tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, azetidyl,        pyrrolidyl, piperidyl, hexahydroazepinyl, thietanyl, thiolanyl,        tetrahydrothiopyranyl, thiepanyl, 1,4-oxathianyl,        1,3-dioxolanyl, 1,2-dithiolanyl, 1,3-dithiolanyl,        hexahydro-pyridazinyl, imidazolidyl, 1,3-dioxanyl, morpholinyl,        1,3-dithianyl, 1,4-dioxanyl, 1,4-dithianyl, or thiomorpholinyl,        each of which is optionally substituted with one or more        substituents independently selected from R⁷¹, wherein R⁷¹ is as        defined in embodiment A1.        Embodiment A237. A compound according to embodiment A236 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are        tetrahydropyranyl, oxepanyl, piperidyl, hexahydroazepinyl,        tetrahydrothiopyranyl, thiepanyl, 1,4-oxathianyl,        1,3-dithiolanyl, hexahydro-pyridazinyl, 1,3-dioxanyl,        morpholinyl, 1,3-dithianyl, 1,4-dioxanyl, 1,4-dithianyl, or        thiomorpholinyl, each of which is optionally substituted with        one or more substituents independently selected from R⁷¹,        wherein R⁷¹ is as defined in embodiment A1.        Embodiment A238. A compound according to embodiment A237 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are        tetrahydropyranyl, piperidyl, tetrahydrothiopyranyl,        1,4-oxathianyl, hexahydro-pyridazinyl, morpholinyl,        1,4-dioxanyl, 1,4-dithianyl, or thiomorpholinyl, each of which        is optionally substituted with one or more substituents        independently selected from R⁷¹, wherein R⁷¹ is as defined in        embodiment A1.        Embodiment A239. A compound according to embodiment A238 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are        tetrahydropyranyl, piperidyl, tetrahydrothiopyranyl, or        morpholinyl, each of which is optionally substituted with one or        more substituents independently selected from R⁷¹, wherein R⁷¹        is as defined in embodiment A1.        Embodiment A240. A compound according to embodiment A239 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are piperidyl or        morpholinyl, each of which is optionally substituted with one or        more substituents independently selected from R⁷¹, wherein R⁷¹        is as defined in embodiment A1.        Embodiment A241. A compound according to embodiment A240 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are piperidyl or        morpholinyl.

242.

Embodiment A243. A compound according to any one of the embodiments A1to A230 wherein

-   -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are furanyl,        thienyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl,        tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl,        thiadiazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrazinyl,        pyrimidinyl, quinolinyl, isoquinolinyl, benzofuranyl,        benzothiophenyl, indolyl, purinyl, or indazolyl, each of which        is optionally substituted with one or more substituents        independently selected from R⁷¹, wherein R⁷¹ is as defined in        embodiment A1.        Embodiment A244. A compound according to embodiment A243 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are furanyl,        thienyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl,        tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl,        thiadiazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrazinyl,        pyrimidinyl, benzofuranyl, indolyl, or purinyl, each of which is        optionally substituted with one or more substituents        independently selected from R⁷¹, wherein R⁷¹ is as defined in        embodiment A1.        Embodiment A245. A compound according to embodiment A244,        wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are imidazolyl,        triazolyl, tetrazolyl, thiazolyl, pyridinyl, pyrimidinyl,        benzofuranyl, indolyl, or purinyl, each of which is optionally        substituted with one or more substituents independently selected        from R⁷¹, wherein R⁷¹ is as defined in embodiment A1.        Embodiment A246. A compound according to embodiment A245 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are imidazolyl,        triazolyl, tetrazolyl, thiazolyl, pyridinyl, pyrimidinyl, or        purinyl, each of which is optionally substituted with one or        more substituents independently selected from R⁷¹, wherein R⁷¹        is as defined in embodiment A1.        Embodiment A247. A compound according to embodiment A246 wherein    -   R⁵⁴, R⁵⁵ and R⁵⁶ independently of each other are imidazolyl,        triazolyl, tetrazolyl, thiazolyl, pyridinyl, pyrimidinyl, each        of which is optionally substituted with one or more substituents        independently selected from R⁷¹, wherein R⁷¹ is as defined in        embodiment A1.        Embodiment A248. A compound according to embodiment A247 wherein        R⁵⁴ is imidazolyl optionally substituted with one or more        substituents independently selected from R⁷¹, wherein R⁷¹ is as        defined in embodiment A1.        Embodiment A249. A compound according to embodiment A247 wherein        R⁵⁴ is triazolyl optionally substituted with one or more        substituents independently selected from R⁷¹, wherein R⁷¹ is as        defined in embodiment A1.        Embodiment A250. A compound according to embodiment A247 wherein        R⁵⁴ is tetrazolyl optionally substituted with one or more        substituents independently selected from R⁷¹, wherein R⁷¹ is as        defined in embodiment A1.        Embodiment A251. A compound according to embodiment A247 wherein        R⁵⁴ is thiazolyl optionally substituted with one or more        substituents independently selected from R⁷¹, wherein R⁷¹ is as        defined in embodiment A1.        Embodiment A252. A compound according to embodiment A247 wherein        R⁵⁴ is pyridinyl optionally substituted with one or more        substituents independently selected from R⁷¹, wherein R⁷¹ is as        defined in embodiment A1.        Embodiment A253. A compound according to embodiment A247 wherein        R⁵⁴ is pyrimidinyl optionally substituted with one or more        substituents independently selected from R⁷¹, wherein R⁷¹ is as        defined in embodiment A1.        Embodiment A254. A compound according to embodiment A246 wherein        R⁵⁴ is purinyl optionally substituted with one or more        substituents independently selected from R⁷¹, wherein R⁷¹ is as        defined in embodiment A1.        Embodiment A255. A compound according to any one of the        embodiments A1 to A254 wherein R⁷¹ is methyl or ═O.        Embodiment A256. A compound according to any one of the        embodiments A1 to A254 wherein R⁷¹ is —C(O)OH        Embodiment A257. A compound according to any one of the        embodiments A1 to A254 wherein R⁷¹ is —(CH₂)₁₋₃C(O)OH.        Embodiment A258. A compound according to any one of the        embodiments A1 to A254 wherein R⁷⁰ is —(CH₂)₁₋₃NR⁷⁵R⁷⁶.        Embodiment A259. A compound according to any one of the        embodiments A1 to A230 wherein u is 0 or 1.        Embodiment A260. A compound according to embodiment A259 wherein        u is 0.        Embodiment A261. A compound according to embodiment A259 wherein        u is 1.        Embodiment A262. A compound according to any one of the        embodiments A1 to A230 wherein v is 0 or 1.        Embodiment A263. A compound according to embodiment A262 wherein        v is 0.        Embodiment A264. A compound according to embodiment A262 wherein        v is 1′.        Embodiment A265. A compound according to any one of the        embodiments A1 to A230 wherein u is 0 and v is 1.        Embodiment A266. A compound according to any one of the        embodiments A1 to A230 wherein u and v are both 0.        Embodiment A267. A compound according to any one of the        embodiments A1 to A230 or A259 to A266 wherein R⁷² and R⁷³ are        independently selected from hydrogen, hydroxy or —C(O)OR⁷⁵.        Embodiment A268. A compound according to embodiment A267 wherein        R⁷² and R⁷³ are independently selected from hydrogen or        —C(O)OR⁷⁵, wherein R⁷⁵ is as defined in embodiment A1.        Embodiment A269. A compound according to embodiment A267 wherein        R⁷² and R⁷³ are hydrogen.        Embodiment A270. A compound according to any one of the        embodiments A1 to A230 or A259 to A269 wherein    -   W⁶ is —O—R⁷⁵, —C(O)O—R⁷⁵, —C(O)—R⁷⁵, —NR⁷⁵R⁷⁶, —NHCH₂C(O)R⁷⁵,        —NHC(O)R⁷⁵, —S(O)₂R⁷⁵, —NHS(O)₂R⁷⁵ or    -   W⁶ is heterocyclyl, wherein R⁷⁵ and R⁷⁶ are as defined in        embodiment A1.        Embodiment A271. A compound according to embodiment A270 wherein    -   W⁶ is —O—R⁷⁵, —C(O)O—R⁷⁵, —C(O)—R⁷⁵, —NR⁷⁵R⁷⁶, —NHCH₂C(O)R⁷⁵,        —NHC(O)R⁷⁵, —S(O)₂R⁷⁵, —NHS(O)₂R⁷⁵, or    -   W⁶ is oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl,        azetidyl, pyrrolidyl, piperidyl, hexahydroazepinyl, thietanyl,        thiolanyl, tetrahydrothiopyranyl, thiepanyl, 1,4-oxathianyl,        1,3-dioxolanyl, 1,2-dithiolanyl, 1,3-dithiolanyl,        hexahydro-pyridazinyl, imidazolidyl, 1,3-dioxanyl, morpholinyl,        1,3-dithianyl, 1,4-dioxanyl, 1,4-dithianyl, or thiomorpholinyl,        wherein R⁷⁵ and R⁷⁶ are as defined in embodiment A1.        Embodiment A272. A compound according to embodiment A270 wherein    -   W⁶ is —O—R⁷⁵, —C(O)O—R⁷⁵, —C(O)—R⁷⁵, —NR⁷⁵R⁷⁶, —NHCH₂C(O)R⁷⁵,        —NHC(O)R¹⁵, —S(O)₂R⁷⁵, —NHS(O)₂R⁷⁵, or    -   W⁶ is tetrahydropyranyl, oxepanyl, piperidyl, hexahydroazepinyl,        tetrahydrothiopyranyl, thiepanyl, 1,4-oxathianyl, morpholinyl,        1,4-dioxanyl, 1,4-dithianyl, or thiomorpholinyl, wherein R⁷⁵ and        R⁷⁶ are as defined in embodiment A1.        Embodiment A273. A compound according to embodiment A272 wherein    -   W⁶ is —O—R⁷⁵, —C(O)O—R⁷⁵, —C(O)—R⁷⁵, —NR⁷⁵R⁷⁶, —NHCH₂C(O)R⁷⁵,        —NHC(O)R⁷⁵, —S(O)₂R⁷⁵, —NHS(O)₂R⁷⁵, or    -   W⁶ is tetrahydropyranyl, piperidyl, tetrahydrothiopyranyl, or        morpholinyl, wherein R⁷⁵ and R⁷⁶ are as defined in embodiment        A1.        Embodiment A274. A compound according to embodiment A273 wherein    -   W⁶ is —O—R⁷⁵, —C(O)O—R⁷⁵, —NR⁷⁵R⁷⁶, —NHC(O)R⁷⁵, —S(O)₂R⁷⁵, or    -   W⁶ is tetrahydropyranyl, piperidyl, tetrahydrothiopyranyl, or        morpholinyl,    -   wherein R⁷⁵ and R⁷⁶ are as defined in embodiment A1.        Embodiment A275. A compound according to embodiment A274 wherein    -   W⁶ is —O—R⁷⁵, or —C(O)O—R⁷⁵, wherein R⁷⁵ is as defined in        embodiment A1.        Embodiment A276. A compound according to embodiment A275 wherein        W⁶ is —C(O)O—R⁷⁵, wherein R⁷⁵ is as defined in embodiment A1.        Embodiment A277. A compound according to any one of the        embodiments A1 to A230 or A259 to A276 wherein R⁷⁵ and R⁷⁶ are        independently selected from hydrogen, —OH, or C₁₋₆-alkyl        optionally substituted with —NH₂.        Embodiment A278. A compound according to embodiment A277 wherein        R⁷⁵ and R⁷⁶ are independently selected from hydrogen, —OH, or        methyl.        Embodiment A279. A compound according to embodiment A278 wherein        R⁷⁵ and R⁷⁶ are independently selected from hydrogen or —OH.        Embodiment A280. A compound according to embodiment A279 wherein        R⁷⁵ is hydrogen.        Embodiment A281. A compound according to any one of the        embodiments A1 to A280, which compound is an activator of        glucokinase, when tested in the Glucokinase Activation Assay (I)        disclosed herein at a glucose concentration of 2 mM.        Embodiment A282. A compound according to any one of the        embodiments A1 to A281, which compound is an activator of        glucokinase, when tested in the Glucokinase Activation Assay (I)        disclosed herein at a glucose concentration of from 10 to 15 mM.        Embodiment A283. A compound according to any one of the        embodiments A1 to A282, which compound, at a concentration of 30        μM, is capable of providing an at least 1.5, such as at least        1.7, for instance at least 2.0 fold activation of glucokinase in        the Glucokinase Activation Assay (I) disclosed herein at a        glucose concentration of 2 mM.        Embodiment A284. A compound according to any one of the        embodiments A1 to A283, which compound, at a concentration of 30        μM, is capable of providing an at least 1.5, such as at least        1.7, for instance at least 2.0 fold activation of glucokinase in        the Glucokinase Activation Assay (I) disclosed herein at a        glucose concentration of from 10 to 15 mM.        Embodiment A285. A compound according to any one of the        embodiments A1 to A284, which at a concentration of 5 μM is        capable of providing an at least 1.5, such as at least 1.7, for        instance at least 2.0 fold activation of glucokinase in the        Glucokinase Activation Assay (I) disclosed herein at a glucose        concentration of 2 mM.        Embodiment A286. A compound according to any one of the        embodiments A1 to A285, which at a concentration of 5 μM is        capable of providing an at least 1.5, such as at least 1.7, for        instance at least 2.0 fold activation of glucokinase in the        Glucokinase Activation Assay (I) disclosed herein at a glucose        concentration of from 10 to 15 mM.        Embodiment A287. A glucose kinase activator compound defined as        a compound which at a compound concentration of at or below 30        μM at a glucose concentration of 2 mM in the Glucokinase        Activation Assay (I) disclosed herein gives 1.5-fold higher        glucokinase activity than measured at a glucose concentration of        2 mM in the Glucokinase Activation Assay (I) without compound,        where the increase in glucokinase activity provided by the        compound increases with increasing concentrations of glucose.        Embodiment A288. A compound according to any one of the        embodiments A1 to A286, which compound provides an increase in        glucokinase activity, where the increase in glucokinase activity        provided by the compound increases with increasing        concentrations of glucose.        Embodiment A289. A compound according to embodiment A287 or        embodiment A288, which provides an increase in glucokinase        activity in Glucokinase Activation Assay (I) disclosed herein at        a glucose concentration of 15 mM, which increase is        significantly higher than the increase in glucokinase activity        provided by the compound in Glucokinase Activation Assay (I)        disclosed herein at a glucose concentration of 5 mM.        Embodiment A290. A compound according to any one of the        embodiments A287 to A289, which at a compound concentration of        10 μM provides an increase in glucokinase activity in        Glucokinase Activation Assay (I) disclosed herein at a glucose        concentration of 15 mM, which increase is significantly higher        than the increase in glucokinase activity provided by the        compound at a compound concentration of 10 μM in Glucokinase        Activation Assay (I) disclosed herein at a glucose concentration        of 5 mM.        Embodiment A291. A compound according to any one of the        embodiments A287 to A290, which at a compound concentration of        10 μM provides an increase in glucokinase activity in        Glucokinase Activation Assay (I) disclosed herein at a glucose        concentration of 15 mM, which increase is at least 1.1 fold        higher, such as at least 1.2 fold higher, for instance at least        1.3 fold higher, such as at least 1.4 fold higher, for instance        1.5 fold higher, such as at least 1.6 fold higher, for instance        at least 1.7 fold higher, such as at least 1.8 fold higher, for        instance at least 1.9 fold higher, such as at least 2.0 fold        higher than the increase in glucokinase activity provided by the        compound at a compound concentration of 10 μM in Glucokinase        Activation Assay (I) disclosed herein at a glucose concentration        of 5 mM.        Embodiment A292. A glucose kinase activator compound defined as        a compound which at a compound concentration of at or below 30        μM at a glucose concentration of 2 mM in the Glucokinase        Activation Assay (I) disclosed herein gives 1.5-fold higher        glucokinase activity than measured at a glucose concentration of        2 mM in the Glucokinase Activation Assay (I) without compound,        which glucose kinase activator compound increases glucose        utilization in the liver without inducing any increase in        insulin secretion in response to glucose.        Embodiment A293. A glucose kinase activator compound defined as        a compound which at a compound concentration of at or below 30        μM at a glucose concentration of 2 mM in the Glucokinase        Activation Assay (I) disclosed herein gives 1.5-fold higher        glucokinase activity than measured at a glucose concentration of        2 mM in the Glucokinase Activation Assay (I) without compound,        which glucokinase activator compound shows a significantly        higher activity in isolated hepatocytes compared to the activity        of the glucokinase compound in Ins-1 cells.        Embodiment A294. A compound according to any one of the        embodiments A1 to A291, which compound increases glucose        utilization in the liver without inducing any increase in        insulin secretion in response to glucose.        Embodiment A295. A compound according to any one of the        embodiments A1 to A291, which compound shows a significantly        higher activity in isolated hepatocytes compared to the activity        of the compound in Ins-1 cells.        Embodiment A296. A compound according to any one of the        embodiments A292 to A295, which compound shows a significantly        higher activity in isolated hepatocytes measured as described in        the Glucokinase Activity Assay (II) compared to the activity of        the compound in Ins-1 cells measured as described in the        Glucokinase Activity Assay (III).        Embodiment A297. A compound according to embodiment A296, which        compound shows an activity in isolated hepatocytes measured as        described in the Glucokinase Activity Assay (II) which activity        is at least 1.1 fold higher, such as at least 1.2 fold higher,        for instance at least 1.3 fold higher, such as at least 1.4 fold        higher, for instance 1.5 fold higher, such as at least 1.6 fold        higher, for instance at least 1.7 fold higher, such as at least        1.8 fold higher, for instance at least 1.9 fold higher, such as        at least 2.0 fold higher, for instance at least a 3.0 fold        higher, such as at least a 4.0 fold higher, for instance at        least 5.0 fold higher, such as at least 10 fold higher than the        activity of the compound in Ins-1 cells measured as described in        the Glucokinase Activity Assay (III).        Embodiment A298. A compound according to embodiment A296, which        compound shows no activity in the Ins-1 cells measured as        described in the Glucokinase Activity Assay (III).        Embodiment A299. A method of preventing hypoglycaemia comprising        administration of a compound according to any one of the        embodiments A1 to A298.        Embodiment A300. The use of a compound according to any one of        the embodiments A1 to        Embodiment A298 for the preparation of a medicament for the        prevention of hypoglycaemia.        Embodiment A301. A compound according to any one of embodiments        A1 to A298, which is an agent useful for the treatment of an        indication selected from the group consisting of hyperglycemia,        IGT, insulin resistance syndrome, syndrome X, type 2 diabetes,        type 1 diabetes, dyslipidemia, hypertension, and obesity.        Embodiment A302. A compound according to any one of embodiments        A1 to A301 for use as a medicament.        Embodiment A303. A compound according to any one of embodiments        A1 to A301 for treatment of hyperglycemia, for treatment of IGT,        for treatment of Syndrome X, for treatment of type 2 diabetes,        for treatment of type 1 diabetes, for treatment of dyslipidemia,        for treatment of hyperlipidemia, for treatment of hypertension,        for treatment of obesity, for lowering of food intake, for        appetite regulation, for regulating feeding behaviour, or for        enhancing the secretion of enteroincretins, such as GLP-1.        Embodiment A304. A pharmaceutical composition comprising, as an        active ingredient, at least one compound according to any one of        embodiments A1 to 303 together with one or more pharmaceutically        acceptable carriers or excipients.        Embodiment A305. A pharmaceutical composition according to        embodiment A304 in unit dosage form, comprising from about 0.05        mg to about 1000 mg, preferably from about 0.1 mg to about 500        mg and especially preferred from about 0.5 mg to about 200 mg of        the compound according to any one of embodiments A1 to 303.        Embodiment A306. Use of a compound according to any one of the        embodiments A1 to 303 for increasing the activity of        glucokinase.        Embodiment A307. Use of a compound according to any one of        embodiments A1 to A303 for the preparation of a medicament for        the treatment of metabolic disorders, for blood glucose        lowering, for the treatment of hyperglycemia, for the treatment        of IGT, for the treatment of Syndrome X, for the treatment of        impaired fasting glucose (IFG), for the treatment of type 2        diabetes, for the treatment of type 1 diabetes, for delaying the        progression of impaired glucose tolerance (IGT) to type 2        diabetes, for delaying the progression of non-insulin requiring        type 2 diabetes to insulin requiring type 2 diabetes, for the        treatment of dyslipidemia, for the treatment of hyperlipidemia,        for the treatment of hypertension, for lowering of food intake,        for appetite regulation, for the treatment of obesity, for        regulating feeding behaviour, or for enhancing the secretion of        enteroincretins.        Embodiment A308. Use of a compound according to any one of        embodiments A1 to A303 for the preparation of a medicament for        the adjuvant treatment of type 1 diabetes for preventing the        onset of diabetic complications.        Embodiment A309. Use of a compound according to any one of        embodiments A1 to A303 for the preparation of a medicament for        increasing the number and/or the size of beta cells in a        mammalian subject, for treatment of beta cell degeneration, in        particular apoptosis of beta cells, or for treatment of        functional dyspepsia, in particular irritable bowel syndrome.        Embodiment A310. Use according to any one of the embodiments        A307 to A309 in a regimen which comprises treatment with a        further antidiabetic agent.        Embodiment A311. Use according to any one of the embodiments        A307 to A310 in a regimen which comprises treatment with a        further antihyperlipidemic agent.        Embodiment A312. Use according to any one of embodiments A307 to        A311 in a regimen which comprises treatment with a further        antiobesity agent.        Embodiment A313. Use according to any one of embodiments A307 to        A312 in a regimen which comprises treatment with a further        antihypertensive agent.        Embodiment A314. Use of a compound according to any one of the        embodiments A1 to A303 or a pharmaceutical composition according        to embodiment A304 or embodiment A305 for the treatment of        metabolic disorders, for blood glucose lowering, for the        treatment of hyperglycemia, for treatment of IGT, for treatment        of Syndrome X, for the treatment of impaired fasting glucose        (IFG), for treatment of type 2 diabetes, for treatment of type 1        diabetes, for delaying the progression of impaired glucose        tolerance (IGT) to type 2 diabetes, for delaying the progression        of non-insulin requiring type 2 diabetes to insulin requiring        type 2 diabetes, for treatment of dyslipidemia, for treatment of        hyperlipidemia, for treatment of hypertension, for the treatment        or prophylaxis of obesity, for lowering of food intake, for        appetite regulation, for regulating feeding behaviour, or for        enhancing the secretion of enteroincretins.        Embodiment A315. Use of a compound according to any one of the        embodiments A1 to A303 or a pharmaceutical composition according        to embodiment A304 or embodiment A305 for the adjuvant treatment        of type 1 diabetes for preventing the onset of diabetic        complications.        Embodiment A316. Use of a compound according to any one of the        embodiments A1 to A303 or a pharmaceutical composition according        to embodiment A304 or embodiment A305 for increasing the number        and/or the size of beta cells in a mammalian subject, for        treatment of beta cell degeneration, in particular apoptosis of        beta cells, or for treatment of functional dyspepsia, in        particular irritable bowel syndrome.

Further embodiments are clear from the appended claims.

Included within the scope of the present invention are the individualenantiomers of the compounds represented by formula (I) above as well asany wholly or partially racemic mixtures thereof. The present inventionalso covers the individual enantiomers of the compounds represented byformula (I) above as mixtures with diastereoisomers thereof in which oneor more stereocenters are inverted.

The present invention provides glucose sensitive glucokinase activators,that is glucokinase activators, for instance of the general formula (I),which provides a higher increase in glucokinase activity at lowerconcentrations of glucose. This should be taken to mean that when theglucose concentration is low, then the glucose sensitive glucokinaseactivator provides an increase in the glucokinase activity, whichincrease is higher than the increase in glucokinase activity provided bythe compound when glucose concentration is high. The compound may forinstance provide a 4.0 fold increase in glucokinase activity at aglucose concentration of 5 mM and a 2.0 fold increase in glucokinaseactivity at a glucose concentration of 15 mM, thus providing an increasein glucokinase activity at a glucose concentration of 5 mM, whichincrease is 2.0 fold higher than the increase in glucokinase activityprovided by the compound at a glucose concentration of 15 mM. For thepurpose of describing the present invention, the glucose sensitivity maybe assayed by use of Glucokinase Activity Assay (I) where the activityof the glucokinase activator is measured at different concentrations ofglucose.

The glucose sensitivity of a glucokinase activator may for instance bemeasured at a glucose concentration of 5 mM and at a glucoseconcentration of 15 mM using the same concentration of glucokinaseactivator, such as a concentration of 10 μM. The two measurements maythen be compared and if the fold activity at a glucose concentration of5 mM (the lower glucose concentration)—in the above example 4.0 fold—issignificantly higher than the fold activity at a glucose concentrationof 15 mM (the higher glucose concentration—in the above example 2.0fold—then the glucokinase activator is deemed to be a glucose sensitiveglucokinase activator. In the above example, the increase in glucokinaseactivity at a glucose concentration of 5 mM is 2.0 fold higher than theincrease in glucokinase activity at a glucose concentration of 15 mM.The increase in glucokinase activity provided by the glucokinaseactivator at 5 mM glucose may for instance be at least 1.1 fold higher,such as at least 1.2 fold higher, for instance at least 1.3 fold higher,such as at least 1.4 fold higher, for instance 1.5 fold higher, such asat least 1.6 fold higher, for instance at least 1.7 fold higher, such asat least 1.8 fold higher, for instance at least 1.9 fold higher, such asat least 2.0 fold higher than the activity of the glucokinase activatorat 15 mM glucose.

The present invention provides liver specific glucokinase activators,that is, glucokinase activators, for instance of the general formula(I), which increase glucose utilization in the liver (i.e. increaseglycogen deposition) without inducing any increase in insulin secretionin response to glucose. For the purpose of describing this invention,the potential liver selectivity of a glucokinase activator may beassayed by comparison of the results obtained in response to theglucokinase activator in isolated hepatocytes and the results obtainedin response to the glucokinase activator in Ins-1 cells. Glucokinaseactivators, which show a significantly higher activity in isolatedhepatocytes measured as described in the Glucokinase Activity Assay (II)compared to the activity in Ins-1 cells measured as described in theGlucokinase Activity Assay (III), are deemed to be liver specificglucokinase activators. The activity of the glucokinase activator inGlucokinase Activity Assay (II) (hepatocytes) may for instance be atleast 1.1 fold higher, such as at least 1.2 fold higher, for instance atleast 1.3 fold higher, such as at least 1.4 fold higher, for instance1.5 fold higher, such as at least 1.6 fold higher, for instance at least1.7 fold higher, such as at least 1.8 fold higher, for instance at least1.9 fold higher, such as at least 2.0 fold higher, for instance at leasta 3.0 fold higher, such as at least a 4.0 fold higher, for instance atleast 5.0 fold higher, such as at least 10 fold higher than the activityof the glucokinase activator in Glucokinase Activity Assay (III) (Ins-1cells). Alternatively, the glucokinase activator may show no activity inthe Ins-1 cells measured as described in the Glucokinase Activity Assay(III), while showing a significant activity in hepatocytes measured asdescribed in the Glucokinase Activity Assay (II).

Such liver-specific glucokinase activators may be particularly useful inpatients that are at risk of experiencing hypoglycaemia. Since liverglucokinase is highly sensitive to the serum concentration of glucose,the blood glucose-decreasing effect of the GK in the liver will onlyoccur when the serum concentration of glucose is relatively high. Whenthe serum concentration of glucose is relatively low, the effect of theGK in the liver decreases, and thus does not further lower the glucoseconcentration in the blood. This mechanism remains even when the liverGK is affected by a GK activator. The effect of GK on the pancreaticbeta cells is not similarly glucose-sensitive. Therefore a GK activatorwhich affects both liver and beta cells may have a glucose-loweringeffect even at low serum glucose concentration, resulting in a risk ofhypoglycaemia. A GK activator which affects only, or which primarilyeffects, the liver GK will thus provide a treatment with a lower risk ofhypoglycaemia. Thus the invention provides a method of preventinghypoglycaemia comprising administration of a liver-specific glucokinaseactivator, as well as the use of a liver-specific glucokinase activatorfor the preparation of a medicament for the prevention of hypoglycaemia.

Examples of liver specific glucokinase activators are

-   2-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazole-4-carboxylic    acid ethyl ester,-   (2-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazol-4-yl)acetic    acid ethyl ester,-   (2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)acetic    acid,-   2-{3-[2-(2,3-dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazole-4-carboxylic    acid,-   2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)-N-(2-morpholin-4-ylethyl)acetamide,-   [2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)acetylamino]acetic    acid,-   {2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid, and-   {2-[3-(4-methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-acetic    acid.

In one embodiment, a compound according to the present invention is foruse as a medicament in the treatment of hyperglycemia.

In one embodiment, a compound according to the present invention is foruse as a medicament in the treatment of IGT.

In one embodiment, a compound according to the present invention is foruse as a medicament in the treatment of Syndrome X.

In one embodiment, a compound according to the present invention is foruse as a medicament in the treatment of type 2 diabetes.

In one embodiment, a compound according to the present invention is foruse as a medicament in the treatment of type 1 diabetes.

In one embodiment, a compound according to the present invention is foruse as a medicament in the treatment of hyperlipidemia.

In one embodiment, a compound according to the present invention is foruse as a medicament in the treatment of dyslipidemia.

In one embodiment, a compound according to the present invention is foruse as a medicament in the treatment of hypertension.

In one embodiment, a compound according to the present invention is foruse as a medicament in the treatment of obesity.

In one embodiment, a compound according to the present invention is foruse as a medicament for lowering of food intake.

In one embodiment, a compound according to the present invention is foruse as a medicament for appetite regulation.

In one embodiment, a compound according to the present invention is foruse as a medicament for regulating feeding behaviour.

In one embodiment, a compound according to the present invention is foruse as a medicament for enhancing the secretion of enteroincretins, suchas GLP-1.

The present compounds are activators of glucokinase and are as suchuseful for the activation of glucokinase.

Accordingly, the present invention provides a method for activatingglucokinase in a patient in need thereof, which method comprisesadministering to a subject in need thereof a compound according to thepresent invention, preferably in a pharmacologically effective amount,more preferably in a therapeutically effective amount. The presentinvention also provides a method for lowering blood glucose in a patientin need thereof, which method comprises administering to a subject inneed thereof a compound according to the present invention, preferablyin a pharmacologically effective amount, more preferably in atherapeutically effective amount. The present invention also provides amethod for prevention and/or treatment of glucokinasedeficiency-mediated human diseases, the method comprising administrationto a human in need thereof a therapeutically effective amount of acompound according to the present invention. As used herein, the phrase“a subject in need thereof” includes mammalian subjects, preferablyhumans, who either suffer from one or more of the aforesaid diseases ordisease states or are at risk for such. Accordingly, in the context ofthe therapeutic method of the present invention, this method also iscomprised of a method for treating a mammalian subject prophylactically,or prior to the onset of diagnosis such disease(s) or disease state(s).

In one embodiment, the present invention provides a method for thetreatment of hyperglycemia, the method comprising administering to asubject in need thereof an effective amount of a compound or apharmaceutical composition according to the present invention.

In one embodiment, the present invention provides a method for thetreatment of IGT, the method comprising administering to a subject inneed thereof an effective amount of a compound or a pharmaceuticalcomposition according to the present invention.

In one embodiment, the present invention provides a method for thetreatment of Syndrome X, the method comprising administering to asubject in need thereof an effective amount of a compound or apharmaceutical composition according to the present invention.

In one embodiment, the present invention provides a method for thetreatment of type 2 diabetes, the method comprising administering to asubject in need thereof an effective amount of a compound or apharmaceutical composition according to the present invention.

In one embodiment, the present invention provides a method for thetreatment of type 1 diabetes, the method comprising administering to asubject in need thereof an effective amount of a compound or apharmaceutical composition according to the present invention.

In one embodiment, the present invention provides a method for thetreatment of dyslipidemia or hyperlipidemia, the method comprisingadministering to a subject in need thereof an effective amount of acompound or a pharmaceutical composition according to the presentinvention.

In one embodiment, the present invention provides a method for thetreatment of obesity, the method comprising administering to a subjectin need thereof an effective amount of a compound or a pharmaceuticalcomposition according to the present invention.

In one embodiment, the effective amount of the compound is in the rangeof from about 0.05 mg to about 2000 mg, preferably from about 0.1 mg toabout 1000 mg and especially preferred from about 0.5 mg to about 500 mgper day.

In one embodiment, the method according to the present invention is partof a regimen, which comprises treatment with a further antidiabeticagent, for example an antidiabetic agent such as insulin or an insulinanalogue, a sulphonylurea, a biguanide, a meglitinide, an insulinsensitizer, a thiazolidinedione insulin sensitizer, an α-glucosidaseinhibitor, a glycogen phosphorylase inhibitor, or an agent acting on theATP-dependent potassium channel of the pancreatic β-cells.

In one embodiment, the method according to the present invention is partof a regimen, which comprises treatment with a furtherantihyperlipidemic agent, for example an antihyperlipidemic agent suchas cholestyramine, colestipol, clofibrate, gemfibrozil, lovastatin,pravastatin, simvastatin, probucol or dextrothyroxine.

In one embodiment, the method according to the present invention is partof a regimen, which comprises treatment with a further antihypertensiveagent.

In one embodiment, the method according to the present invention is partof a regimen, which comprises treatment with a further antiobesity orappetite regulating agent.

In one embodiment, the method according to the present invention is partof a regimen, which comprises treatment with a further antihypertensiveagent.

Other embodiments of such methods will be clear from the followingdescription.

Compounds according to the present invention are useful for thetreatment of disorders, diseases and conditions, wherein the activationof glucokinase is beneficial.

Accordingly, the present compounds are useful for the treatment ofhyperglycemia, IGT (impaired glucose tolerance), insulin resistancesyndrome, syndrome X, type 1 diabetes, type 2 diabetes, dyslipidemia,dyslipoproteinemia (abnormal lipoproteins in the blood) includingdiabetic dyslipidemia, hyperlipidemia, hyperlipoproteinemia (excess oflipoproteins in the blood) including type I, II-a(hypercholesterolemia), II-b, III, IV (hypertriglyceridemia) and V(hypertriglyceridemia) hyperlipoproteinemias, and obesity. Furthermore,they may be useful for the treatment of albuminuria, cardiovasculardiseases such as cardiac hypertrophy, hypertension and arteriosclerosisincluding atherosclerosis; gastrointestinal disorders; acutepancreatitis; and appetite regulation or energy expenditure disorders.Accordingly, in a further aspect the invention relates to a compoundaccording to the present invention for use as a medicament.

The invention also relates to pharmaceutical compositions comprising, asan active ingredient, at least one compound according to the presentinvention together with one or more pharmaceutically acceptable carriersor excipients.

The pharmaceutical composition is preferably in unit dosage form,comprising from about 0.05 mg to about 1000 mg, preferably from about0.1 mg to about 500 mg and especially preferred from about 0.5 mg toabout 200 mg of the compound according to the present invention.

In one embodiment, the pharmaceutical composition according to thepresent invention comprises a further antidiabetic agent, for example anantidiabetic agent such as insulin, an insulin derivative or an insulinanalogue, a sulphonylurea, a biguanide, a meglitinide, an insulinsensitizer, a thiazolidinedione insulin sensitizer, an α-glucosidaseinhibitor, a glycogen phosphorylase inhibitor, or an agent acting on theATP-dependent potassium channel of the pancreatic β-cells.

In one embodiment, the pharmaceutical composition according to thepresent invention comprises a further antihyperlipidemic agent, forexample an antihyperlipidemic agent such as cholestyramine, colestipol,clofibrate, gemfibrozil, lovastatin, pravastatin, simvastatin, probucolor dextrothyroxine.

In one embodiment, the pharmaceutical composition according to thepresent invention comprises a further antiobesity or appetite regulatingagent.

In one embodiment, the pharmaceutical composition according to thepresent invention comprises a further antihypertensive agent.

In one embodiment of the present invention, the pharmaceuticalcomposition according to the present invention comprises a compoundaccording to the present invention in combination with one or more ofthe agents mentioned above eg in combination with metformin and asulphonylurea such as glyburide; a sulphonylurea and acarbose;nateglinide and metformin; acarbose and metformin; a sulfonylurea,metformin and troglitazone; insulin and a sulfonylurea; insulin andmetformin; insulin, metformin and a sulfonylurea; insulin andtroglitazone; insulin and lovastatin; etc.

In one embodiment of the present invention, the present compounds areused for the preparation of a medicament for the treatment ofhyperglycemia. As used herein hyperglycemia is to be taken as generallyunderstood in the art, with reference for example to the Report of theExpert Committee of the Diagnosis and Classification of DiabetesMellitus, published in Diabetes Care 20, 1183-1197, (1997), but isusually taken to mean an elevated plasma glucose level exceeding about110 mg/dl. The present compounds are effective in lowering the bloodglucose both in the fasting and postprandial stage.

In one embodiment of the present invention, the present compounds areused for the preparation of a pharmaceutical composition for thetreatment of IGT.

In one embodiment of the present invention, the present compounds areused for the preparation of a pharmaceutical composition for thetreatment of Syndrome X.

In one embodiment of the present invention, the present compounds areused for the preparation of a pharmaceutical composition for thetreatment of type 2 diabetes. Such treatment includes a treatment forthe purpose of the delaying of the progression from IGT to type 2diabetes as well as delaying the progression from non-insulin requiringtype 2 diabetes to insulin requiring type 2 diabetes.

In one embodiment of the present invention the present compounds areused for the preparation of a pharmaceutical composition for thetreatment of type 1 diabetes. Such therapy is normally accompanied byinsulin administration.

In one embodiment of the present invention the present compounds areused for the preparation of a pharmaceutical composition for thetreatment of dyslipidemia and hyper-lipidemia.

In one embodiment of the present invention the present compounds areused for the preparation of a pharmaceutical composition for thetreatment of obesity.

In another aspect of the present invention treatment of a patient withthe present compounds are combined with diet and/or exercise.

The present invention provides methods of activating glucokinaseactivity in a mammal, which methods comprise administering, to a mammalin need of activation of glucokinase activity, a therapeutically definedamount of a compound according to the present invention defined above,as a single or polymorphic crystalline form or forms, an amorphous form,a single enantiomer, a racemic mixture, a single stereoisomer, a mixtureof stereoisomers, a single diastereoisomer, a mixture ofdiastereoisomers, a solvate, a pharmaceutically acceptable salt, asolvate, a prodrug, a biohydrolyzable ester, or a biohydrolyzable amidethereof.

The present invention provides a method of activating glucokinase,comprising the step of administering to a mammal in need thereof apharmacologically effective amount of a compound according to thepresent invention. The invention further provides a pharmaceuticalcomposition comprising a pharmaceutically acceptable carrier and apharmacologically effective amount of a compound according to thepresent invention sufficient to activate glucokinase. Aglucokinase—activating amount can be an amount that reduces or inhibitsa PTPase activity in the subject.

Additionally provided by the present invention is a pharmaceuticalcomposition comprising a pharmaceutically acceptable carrier and apharmacologically effective amount of a compound according to thepresent invention sufficient to treat type I diabetes.

Also provided by the present invention is a pharmaceutical compositioncomprising a pharmaceutically acceptable carrier and a pharmacologicallyeffective amount of a compound according to the present inventionsufficient to treat type II diabetes.

The compounds of the present invention can be administered to any mammalin need of activation of glucokinase activity. Such mammals can include,for example, horses, cows, sheep, pigs, mice, dogs, cats, primates suchas chimpanzees, gorillas, rhesus monkeys, and, most preferably humans.

In a further aspect of the present invention the present compounds areadministered in combination with one or more further active substancesin any suitable ratios. Such further active agents may be selected fromantidiabetic agents, antihyperlipidemic agents, antiobesity agents,antihypertensive agents and agents for the treatment of complicationsresulting from or associated with diabetes.

Suitable antidiabetic agents include insulin, GLP-1 (glucagon likepeptide-1) derivatives such as those disclosed in WO 98/08871 (NovoNordisk A/S), which is incorporated herein by reference, as well asorally active hypoglycemic agents.

Suitable orally active hypoglycemic agents preferably includeimidazolines, sulfonylureas, biguanides, meglitinides,oxadiazolidinediones, thiazolidinediones, insulin sensitizers,α-glucosidase inhibitors, agents acting on the ATP-dependent potassiumchannel of the pancreatic β-cells eg potassium channel openers such asthose disclosed in WO 97/26265, WO 99/03861 and WO 00/37474 (NovoNordisk A/S) which are incorporated herein by reference, potassiumchannel openers, such as ormitiglinide, potassium channel blockers suchas nateglinide or BTS-67582, glucagon antagonists such as thosedisclosed in WO 99/01423 and WO 00/39088 (Novo Nordisk A/S and AgouronPharmaceuticals, Inc.), all of which are incorporated herein byreference, GLP-1 agonists such as those disclosed in WO 00/42026 (NovoNordisk A/S and Agouron Pharmaceuticals, Inc.), which are incorporatedherein by reference, DPP-IV (dipeptidyl peptidase-IV) inhibitors, PTPase(protein tyrosine phosphatase) inhibitors, inhibitors of hepatic enzymesinvolved in stimulation of gluconeogenesis and/or glycogenolysis,glucose uptake modulators, GSK-3 (glycogen synthase kinase-3)inhibitors, compounds modifying the lipid metabolism such asantihyperlipidemic agents and antilipidemic agents, compounds loweringfood intake, and PPAR (peroxisome proliferator-activated receptor) andRXR (retinoid X receptor) agonists such as ALRT-268, LG-1268 or LG-1069.

In one embodiment of the present invention, the present compounds areadministered in combination with insulin, insulin derivatives or insulinanalogues.

In one embodiment of the present invention, the present compounds areadministered in combination with a sulphonylurea eg tolbutamide,chlorpropamide, tolazamide, glibenclamide, glipizide, glimepiride,glicazide or glyburide.

In one embodiment of the present invention, the present compounds areadministered in combination with a biguanide eg metformin.

In one embodiment of the present invention, the present compounds areadministered in combination with a meglitinide eg repaglinide orsenaglinide/nateglinide.

In one embodiment of the present invention, the present compounds areadministered in combination with a thiazolidinedione insulin sensitizereg troglitazone, ciglitazone, pioglitazone, rosiglitazone, isaglitazone,darglitazone, englitazone, CS-011/CI-1037 or T 174 or the compoundsdisclosed in WO 97/41097 (DRF-2344), WO 97/41119, WO 97/41120, WO00/41121 and WO 98/45292 (Dr. Reddy's Research Foundation), which areincorporated herein by reference.

In one embodiment of the present invention the present compounds may beadministered in combination with an insulin sensitizer eg such as GI262570, YM-440, MCC-555, JTT-501, AR-H039242, KRP-297, GW-409544,CRE-16336, AR-H049020, LY510929, MBX-102, CLX-0940, GW-501516 or thecompounds disclosed in WO 99/19313 (NN622/DRF-2725), WO 00/50414, WO00/63191, WO 00/63192, WO 00/63193 (Dr. Reddy's Research Foundation) andWO 00/23425, WO 00/23415, WO 00/23451, WO 00/23445, WO 00/23417, WO00/23416, WO 00/63153, WO 00/63196, WO 00/63209, WO 00/63190 and WO00/63189 (Novo Nordisk A/S), which are incorporated herein by reference.

In one embodiment of the present invention the present compounds areadministered in combination with an α-glucosidase inhibitor egvoglibose, emiglitate, miglitol or acarbose.

In one embodiment of the present invention the present compounds areadministered in combination with a glycogen phosphorylase inhibitor egthe compounds described in WO 97/09040 (Novo Nordisk A/S).

In one embodiment of the present invention the present compounds areadministered in combination with an agent acting on the ATP-dependentpotassium channel of the pancreatic β-cells eg tolbutamide,glibenclamide, glipizide, glicazide, BTS-67582 or repaglinide.

In one embodiment of the present invention the present compounds areadministered in combination with nateglinide.

In one embodiment of the present invention the present compounds areadministered in combination with an antihyperlipidemic agent or aantilipidemic agent eg cholestyramine, colestipol, clofibrate,gemfibrozil, lovastatin, pravastatin, simvastatin, probucol ordextrothyroxine.

In another aspect of the present invention, the present compounds areadministered in combination with more than one of the above-mentionedcompounds eg in combination with metformin and a sulphonylurea such asglyburide; a sulphonylurea and acarbose; nateglinide and metformin;acarbose and metformin; a sulfonylurea, metformin and troglitazone;insulin and a sulfonylurea; insulin and metformin; insulin, metforminand a sulfonylurea; insulin and troglitazone; insulin and lovastatin;etc.

Furthermore, the compounds according to the invention may beadministered in combination with one or more antiobesity agents orappetite regulating agents.

Such agents may be selected from the group consisting of CART (cocaineamphetamine regulated transcript) agonists, NPY (neuropeptide Y)antagonists, MC3 (melanocortin 3) agonists, MC4 (melanocortin 4)agonists, orexin antagonists, TNF (tumor necrosis factor) agonists, CRF(corticotropin releasing factor) agonists, CRF BP (corticotropinreleasing factor binding protein) antagonists, urocortin agonists, β3adrenergic agonists such as CL-316243, AJ-9677, GW-0604, LY362884,LY377267 or AZ-40140, MSH (melanocyte-stimulating hormone) agonists, MCH(melanocyte-concentrating hormone) antagonists, CCK (cholecystokinin)agonists, serotonin reuptake inhibitors (fluoxetine, seroxat orcitalopram), serotonin and norepinephrine reuptake inhibitors, 5HT(serotonin) agonists, bombesin agonists, galanin antagonists, growthhormone, growth factors such as prolactin or placental lactogen, growthhormone releasing compounds, TRH (thyreotropin releasing hormone)agonists, UCP 2 or 3 (uncoupling protein 2 or 3) modulators, leptinagonists, DA (dopamine) agonists (bromocriptin, doprexin),lipase/amylase inhibitors, PPAR modulators, RXR modulators, TR βagonists, adrenergic CNS stimulating agents, AGRP (agouti relatedprotein) inhibitors, H3 histamine antagonists such as those disclosed inWO 00/42023, WO 00/63208 and WO 00/64884, which are incorporated hereinby reference, exendin-4, GLP-1 agonists and ciliary neurotrophic factor.Further antiobesity agents are bupropion (antidepressant), topiramate(anticonvulsant), ecopipam (dopamine D1/D5 antagonist) and naltrexone(opioid antagonist).

In one embodiment of the present invention the antiobesity agent isleptin.

In one embodiment of the present invention the antiobesity agent is aserotonin and norepinephrine reuptake inhibitor eg sibutramine.

In one embodiment of the present invention the antiobesity agent is alipase inhibitor eg orlistat.

In one embodiment of the present invention the antiobesity agent is anadrenergic CNS stimulating agent eg dexamphetamine, amphetamine,phentermine, mazindol phendimetrazine, diethylpropion, fenfluramine ordexfenfluramine.

Furthermore, the present compounds may be administered in combinationwith one or more antihypertensive agents. Examples of antihypertensiveagents are β-blockers such as alprenolol, atenolol, timolol, pindolol,propranolol and metoprolol, ACE (angiotensin converting enzyme)inhibitors such as benazepril, captopril, enalapril, fosinopril,lisinopril, quinapril and ramipril, calcium channel blockers such asnifedipine, felodipine, nicardipine, isradipine, nimodipine, diltiazemand verapamil, and α-blockers such as doxazosin, urapidil, prazosin andterazosin. Further reference can be made to Remington: The Science andPractice of Pharmacy, 19th Edition, Gennaro, Ed., Mack Publishing Co.,Easton, Pa., 1995.

In a further aspect the invention provides a pharmaceutical preparationcomprising an activator of glucokinase and an insulin derivative.

In one embodiment of the invention the insulin derivative is selectedfrom the group consisting of B29-N^(ε)-myristoyl-des(B30) human insulin,B29-N^(ε)-palmitoyl-des(B30) human insulin, B29-N^(ε)-myristoyl humaninsulin, B29-N^(ε)-palmitoyl human insulin, B28-N^(ε)-myristoylLyS^(B28) Pro^(B29) human insulin, B28-N^(ε)-palmitoyl LyS^(B28)Pro^(B29) human insulin, B30-N^(ε)-myristoyl-Thr^(B29)Lys¹³⁰ humaninsulin, B30-N^(ε)-palmitoyl-Thr^(B29)Lys^(B30) human insulin,B29-N^(ε)-(N-palmitoyl-γ-glutamyl)-des(B30) human insulin,B29-N^(ε)-(N-lithocholyl-γ-glutamyl)-des(B30) human insulin,B29-N^(ε)-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N^(ε)-(ω-carboxyheptadecanoyl) human insulin.

In another embodiment of the invention the insulin derivative isB29-N^(ε)-myristoyl-des(B30) human insulin.

It should be understood that any suitable combination of the compoundsaccording to the invention with diet and/or exercise, one or more of theabove-mentioned compounds and optionally one or more other activesubstances are considered to be within the scope of the presentinvention.

Pharmaceutical Compositions

The compounds of the present invention may be administered alone or incombination with pharmaceutically acceptable carriers or excipients, ineither single or multiple doses. The pharmaceutical compositionsaccording to the invention may be formulated with pharmaceuticallyacceptable carriers or diluents as well as any other known adjuvants andexcipients in accordance with conventional techniques such as thosedisclosed in Remington: The Science and Practice of Pharmacy, 19^(th)Edition, Gennaro, Ed., Mack Publishing Co., Easton, Pa., 1995.

The pharmaceutical compositions may be specifically formulated foradministration by any suitable route such as the oral, rectal, nasal,pulmonary, topical (including buccal and sublingual), transdermal,intracisternal, intraperitoneal, vaginal and parenteral (includingsubcutaneous, intramuscular, intrathecal, intravenous and intradermal)route, the oral route being preferred. It will be appreciated that thepreferred route will depend on the general condition and age of thesubject to be treated, the nature of the condition to be treated and theactive ingredient chosen.

Pharmaceutical compositions for oral administration include solid dosageforms such as hard or soft capsules, tablets, troches, dragees, pills,lozenges, powders and granules. Where appropriate, they can be preparedwith coatings such as enteric coatings or they can be formulated so asto provide controlled release of the active ingredient such as sustainedor prolonged release according to methods well known in the art.

Liquid dosage forms for oral administration include solutions,emulsions, aqueous or oily suspensions, syrups and elixirs.

Pharmaceutical compositions for parenteral administration includesterile aqueous and non-aqueous injectable solutions, dispersions,suspensions or emulsions as well as sterile powders to be reconstitutedin sterile injectable solutions or dispersions prior to use. Depotinjectable formulations are also contemplated as being within the scopeof the present invention.

Other suitable administration forms include suppositories, sprays,ointments, cremes, gels, inhalants, dermal patches, implants etc.

A typical oral dosage is in the range of from about 0.001 to about 100mg/kg body weight per day, preferably from about 0.01 to about 50 mg/kgbody weight per day, and more preferred from about 0.05 to about 10mg/kg body weight per day administered in one or more dosages such as 1to 3 dosages. The exact dosage will depend upon the frequency and modeof administration, the sex, age, weight and general condition of thesubject treated, the nature and severity of the condition treated andany concomitant diseases to be treated and other factors evident tothose skilled in the art.

The formulations may conveniently be presented in unit dosage form bymethods known to those skilled in the art. A typical unit dosage formfor oral administration one or more times per day such as 1 to 3 timesper day may contain from 0.05 to about 1000 mg, preferably from about0.1 to about 500 mg, and more preferred from about 0.5 mg to about 200mg.

For parenteral routes such as intravenous, intrathecal, intramuscularand similar administration, typically doses are in the order of abouthalf the dose employed for oral administration.

The compounds of this invention are generally utilized as the freesubstance or as a pharmaceutically acceptable salt thereof. Examples arean acid addition salt of a compound having the utility of a free baseand a base addition salt of a compound having the utility of a freeacid. The term “pharmaceutically acceptable salts” refers to non-toxicsalts of the compounds of this invention which are generally prepared byreacting the free base with a suitable organic or inorganic acid or byreacting the acid with a suitable organic or inorganic base. When acompound according to the present invention contains a free base suchsalts are prepared in a conventional manner by treating a solution orsuspension of the compound with a chemical equivalent of apharmaceutically acceptable acid. When a compound according to thepresent invention contains a free acid such salts are prepared in aconventional manner by treating a solution or suspension of the compoundwith a chemical equivalent of a pharmaceutically acceptable base.Physiologically acceptable salts of a compound with a hydroxy groupinclude the anion of said compound in combination with a suitable cationsuch as sodium or ammonium ion. Other salts which are notpharmaceutically acceptable may be useful in the preparation ofcompounds of the present invention and these form a further aspect ofthe present invention.

For parenteral administration, solutions of the novel compounds of theformula (I) in sterile aqueous solution, aqueous propylene glycol orsesame or peanut oil may be employed. Such aqueous solutions should besuitably buffered if necessary and the liquid diluent first renderedisotonic with sufficient saline or glucose. The aqueous solutions areparticularly suitable for intravenous, intramuscular, subcutaneous andintraperitoneal administration. The sterile aqueous media employed areall readily available by standard techniques known to those skilled inthe art.

Suitable pharmaceutical carriers include inert solid diluents orfillers, sterile aqueous solution and various organic solvents. Examplesof solid carriers are lactose, terra alba, sucrose, cyclodextrin, talc,gelatine, agar, pectin, acacia, magnesium stearate, stearic acid andlower alkyl ethers of cellulose. Examples of liquid carriers are syrup,peanut oil, olive oil, phospholipids, fatty acids, fatty acid amines,polyoxyethylene and water. Similarly, the carrier or diluent may includeany sustained release material known in the art, such as glycerylmonostearate or glyceryl distearate, alone or mixed with a wax. Thepharmaceutical compositions formed by combining the novel compounds ofthe present invention and the pharmaceutically acceptable carriers arethen readily administered in a variety of dosage forms suitable for thedisclosed routes of administration. The formulations may conveniently bepresented in unit dosage form by methods known in the art of pharmacy.

Formulations of the present invention suitable for oral administrationmay be presented as discrete units such as capsules or tablets, eachcontaining a predetermined amount of the active ingredient, and whichmay include a suitable excipient. Furthermore, the orally availableformulations may be in the form of a powder or granules, a solution orsuspension in an aqueous or non-aqueous liquid, or an oil-in-water orwater-in-oil liquid emulsion.

Compositions intended for oral use may be prepared according to anyknown method, and such compositions may contain one or more agentsselected from the group consisting of sweetening agents, flavoringagents, coloring agents, and preserving agents in order to providepharmaceutically elegant and palatable preparations. Tablets may containthe active ingredient in admixture with non-toxicpharmaceutically-acceptable excipients which are suitable for themanufacture of tablets. These excipients may be for example, inertdiluents, such as calcium carbonate, sodium carbonate, lactose, calciumphosphate or sodium phosphate; granulating and disintegrating agents,for example corn starch or alginic acid; binding agents, for example,starch, gelatin or acacia; and lubricating agents, for example magnesiumstearate, stearic acid or talc. The tablets may be uncoated or they maybe coated by known techniques to delay disintegration and absorption inthe gastrointestinal tract and thereby provide a sustained action over alonger period. For example, a time delay material such as glycerylmonostearate or glyceryl distearate may be employed. They may also becoated by the techniques described in U.S. Pat. Nos. 4,356,108;4,166,452; and 4,265,874, incorporated herein by reference, to formosmotic therapeutic tablets for controlled release.

Formulations for oral use may also be presented as hard gelatin capsuleswhere the active ingredient is mixed with an inert solid diluent, forexample, calcium carbonate, calcium phosphate or kaolin, or a softgelatin capsules wherein the active ingredient is mixed with water or anoil medium, for example peanut oil, liquid paraffin, or olive oil.

Aqueous suspensions may contain the active compounds in admixture withexcipients suitable for the manufacture of aqueous suspensions. Suchexcipients are suspending agents, for example sodiumcarboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose,sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia;dispersing or wetting agents may be a naturally-occurring phosphatidesuch as lecithin, or condensation products of an alkylene oxide withfatty acids, for example polyoxyethylene stearate, or condensationproducts of ethylene oxide with long chain aliphatic alcohols, forexample, heptadecaethyl-eneoxycetanol, or condensation products ofethylene oxide with partial esters derived from fatty acids and ahexitol such as polyoxyethylene sorbitol monooleate, or condensationproducts of ethylene oxide with partial esters derived from fatty acidsand hexitol anhydrides, for example polyethylene sorbitan monooleate.The aqueous suspensions may also contain one or more coloring agents,one or more flavoring agents, and one or more sweetening agents, such assucrose or saccharin.

Oily suspensions may be formulated by suspending the active ingredientin a vegetable oil, for example arachis oil, olive oil, sesame oil orcoconut oil, or in a mineral oil such as a liquid paraffin. The oilysuspensions may contain a thickening agent, for example beeswax, hardparaffin or cetyl alcohol. Sweetening agents such as those set forthabove, and flavoring agents may be added to provide a palatable oralpreparation. These compositions may be preserved by the addition of ananti-oxidant such as ascorbic acid.

Dispersible powders and granules suitable for preparation of an aqueoussuspension by the addition of water provide the active compound inadmixture with a dispersing or wetting agent, suspending agent and oneor more preservatives. Suitable dispersing or wetting agents andsuspending agents are exemplified by those already mentioned above.Additional excipients, for example, sweetening, flavoring, and coloringagents may also be present.

The pharmaceutical compositions of the present invention may also be inthe form of oil-in-water emulsions. The oily phase may be a vegetableoil, for example, olive oil or arachis oil, or a mineral oil, forexample a liquid paraffin, or a mixture thereof. Suitable emulsifyingagents may be naturally-occurring gums, for example gum acacia or gumtragacanth, naturally-occurring phosphatides, for example soy bean,lecithin, and esters or partial esters derived from fatty acids andhexitol anhydrides, for example sorbitan monooleate, and condensationproducts of said partial esters with ethylene oxide, for examplepolyoxyethylene sorbitan monooleate. The emulsions may also containsweetening and flavoring agents.

Syrups and elixirs may be formulated with sweetening agents, for exampleglycerol, propylene glycol, sorbitol or sucrose. Such formulations mayalso contain a demulcent, a preservative and flavoring and coloringagents. The pharmaceutical compositions may be in the form of a sterileinjectible aqueous or oleaginous suspension. This suspension may beformulated according to the known methods using suitable dispersing orwetting agents and suspending agents described above. The sterileinjectable preparation may also be a sterile injectable solution orsuspension in a non-toxic parenterally-acceptable diluent or solvent,for example as a solution in 1,3-butanediol. Among the acceptablevehicles and solvents that may be employed are water, Ringer's solution,and isotonic sodium chloride solution. In addition, sterile, fixed oilsare conveniently employed as solvent or suspending medium. For thispurpose, any bland fixed oil may be employed using synthetic mono- ordiglycerides. In addition, fatty acids such as oleic acid find use inthe preparation of injectables.

The compositions may also be in the form of suppositories for rectaladministration of the compounds of the present invention. Thesecompositions can be prepared by mixing the drug with a suitablenon-irritating excipient which is solid at ordinary temperatures butliquid at the rectal temperature and will thus melt in the rectum torelease the drug. Such materials include cocoa butter and polyethyleneglycols, for example.

For topical use, creams, ointments, jellies, solutions of suspensions,etc., containing the compounds of the present invention arecontemplated. For the purpose of this application, topical applicationsshall include mouth washes and gargles.

The compounds of the present invention may also be administered in theform of liposome delivery systems, such as small unilamellar vesicles,large unilamellar vesicles, and multilamellar vesicles. Liposomes may beformed from a variety of phospholipids, such as cholesterol,stearylamine, or phosphatidylcholines.

In addition, some of the compounds of the present invention may formsolvates with water or common organic solvents. Such solvates are alsoencompassed within the scope of the present invention.

Thus, in a further embodiment, there is provided a pharmaceuticalcomposition comprising a compound according to the present invention, ora pharmaceutically acceptable salt, solvate, or prodrug thereof, and oneor more pharmaceutically acceptable carriers, excipients, or diluents.

If a solid carrier is used for oral administration, the preparation maybe tabletted, placed in a hard gelatine capsule in powder or pellet formor it can be in the form of a troche or lozenge. The amount of solidcarrier will vary widely but will usually be from about 25 mg to about 1g. If a liquid carrier is used, the preparation may be in the form of asyrup, emulsion, soft gelatine capsule or sterile injectable liquid suchas an aqueous or non-aqueous liquid suspension or solution.

A typical tablet that may be prepared by conventional tablettingtechniques may contain: Core: Active compound (as free compound or 5.0mg salt thereof) Lactosum Ph. Eur. 67.8 mg Cellulose, microcryst.(Avicel) 31.4 mg Amberlite ®IRP88* 1.0 mg Magnesii stearas Ph. Eur. q.s.Coating: Hydroxypropyl methylcellulose approx. 9 mg Mywacett 9-40 T**approx. 0.9 mg*Polacrillin potassium NF, tablet disintegrant, Rohm and Haas.**Acylated monoglyceride used as plasticizer for film coating.

If desired, the pharmaceutical composition of the present invention maycomprise a compound according to the present invention in combinationwith further active substances such as those described in the foregoing.

The present invention also provides a method for the synthesis ofcompounds useful as intermediates in the preparation of compounds offormula (I) along with methods for the preparation of compounds offormula (I). The compounds can be prepared readily according to thefollowing reaction Schemes (in which all variables are as definedbefore, unless so specified) using readily available starting materials,reagents and conventional synthesis procedures. In these reactions, itis also possible to make use of variants which are themselves known tothose of ordinary skill in this art, but are not mentioned in greaterdetail.

ABBREVIATIONS

Abbreviations used in the Schemes and Examples are as follows:

-   -   d=days    -   g=grams    -   h=hours    -   Hz=hertz    -   kD=kiloDalton    -   L=liters    -   M=molar    -   mbar=millibar    -   mg=milligrams    -   min=minutes    -   ml=milliliters    -   mM=millimolar    -   mmol=millimoles    -   mol=moles    -   N=normal    -   ppm=parts per million    -   psi=pounds per square inch    -   APCI=atmospheric pressure chemical ionization    -   ESI=electrospray ionization    -   i.v.=intravenous    -   m/z=mass to charge ratio    -   mp=melting point    -   MS=mass spectrometry    -   NMR=nuclear magnetic resonance spectroscopy    -   p.o.=per oral    -   R_(f)=relative TLC mobility    -   rt=room temperature    -   s.c.=subcutaneous    -   TLC=thin layer chromatography    -   t_(r)=retention time    -   BOP=(1-benzotriazolyloxy)tris(dimethylamino)phosphonium        hexafluorophosphate    -   DCM=dichloromethane    -   DIEA=diisopropylethylamine    -   DMF=N,N-dimethylformamide    -   DMPU=1,3-dimethypropylene urea    -   DMSO=dimethylsulfoxide    -   EDC=1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride    -   ether=diethyl ether    -   EtOAc=ethyl acetate    -   HMPA=hexamethylphosphoric triamide    -   HOBt=1-hydroxybenzotriazole    -   LAH=lithium aluminum hydride    -   LDA=lithium diisopropylamide    -   MeOH=methanol    -   NMM=N-methylmorpholine, 4-methylmorpholine    -   TEA=triethylamine    -   TFA=trifluoroacetic acid    -   THF=tetrahydrofuran    -   THP=tetrahydropyranyl    -   TTF=Fluoro-N,N,N′-tetramethylformamidinium hexafluorophosphate        Reaction Schemes

Unless otherwise specified, the variables in the Schemes are as definedfor formula (I).

Scheme 1 describes the preparation of compounds of formula (74).

A² is heteroaryl, fused heterocyclylheteroaryl, or fusedcycloalkylheteroaryl.

R¹⁰⁰ and R¹⁰¹, independently of each other, are substituents such as,but not limited to, H, alkyl, alkenyl, alkynyl, -alkylene-aryl,alkylene-cycloalkyl, and the like.

K is halogen or 1-imidazolyl.

The amine (71) may be treated with carbonyldiimidazole, 4-nitrophenylchloroformate, phosgene or a derivative of phosgene such as diphosgeneor triphosgene, in a solvent such as DCM or DCE. DMAP may be used as acatalyst in this reaction. The reaction may be conducted at atemperature of from 0° C. to 100° C. The reaction mixture may be then betreated with the compound (73) and the whole may be incubated at atemperature of from 25)C to 100° C. to afford the urea (75). It is alsounderstood that (73) may be treated with the reagent (72) under similarconditions, followed by treatment with the amine (71), to afford (74).

Scheme 2 describes the preparation of a compound of formula (79).

-   -   L¹¹ has the meaning of L¹ in formula (I), with the provisio that        when L¹¹ is -D-alkylene-E-, -D-alkenylene-E-, -D-alkynylene-E-,        -D-cycloalkylene-E-, or -D-heterocyclylene-E-, then D is        selected from —O— or —S—, and that L¹¹ is not —S(O)—, —S(O)₂—,        —C(O)—, or —C(═N—OR¹²)—.

Lg¹ is a leaving group such as F, Cl, Br, or I.

R^(10l) is a substituent such as but not limited to H, alkyl, alkenyl,alkynyl, -alkylene-aryl, alkylene-cycloalkyl, and the like.

A nitro-substituted aryl or heteroaryl ring compound such as (75) may betreated with (76) in the presence of a base such as NaH or potassiumtert-butoxide, in a solvent such as THF, DMF, or NMP at a temperature offrom 0° C. to 100° C., to afford (77). The resulting adduct (77) may betreated with tin(II) chloride in ethanol or other alcoholic solvent, ata temperature of from 25° C. to 100° C., in the presence of aqueous HCl,to afford the amine (78). The amine (78) may, is desired, be treatedwith an alkyl halide R¹⁰¹-Lg², wherein Lg² is a leaving group such asBr, I, or p-toluenesulfonate, and a base such as DBU or sodium hydride,to afford (79). Alternatively, (78) may be treated with a reagentR¹⁰²—C(O)—R¹⁰³, wherein R¹⁰² and R¹⁰³ independently of each other aresubstituents such as, but not limited to, H, alkyl, alkenyl, alkynyl,-alkylene-aryl, alkylene-cycloalkyl, and the like, in the presence of areducing agent such as sodium cyanoborohydrode or sodiumtriacetoxyborohydride, to afford (79) wherein R^(10l) should beunderstood as R¹⁰²—C(H)(R¹⁰³)—.

Alternatively, (78) may be treated with a reagent R¹⁰²C(O)—OH in thepresence of a dehydrating agent such as EDC, to afford an intermediateamide, which may be reduced with a reagent such as DIBAL or LAH, in asolvent such as THF, at a temperature of from 0° C. to 80° C., to afford(71) wherein R¹⁰² should be understood as —CH₂—R¹⁰². Alternatively, (79)wherein R¹⁰¹ is —CH₃ may be prepared by treatment of (78) with a reagentR¹⁰²—O—CO—Cl, or R¹⁰²O—CO—O—CO—O—R¹⁰², in the presence of a base such asTEA or aqueous alkali, to afford an intermediate which may be reduced asabove employing DIBAL or LAH giving (79). Compound (79) may be employedin the same manner as is compound (73) according to the chemistry inScheme (1).

Scheme 3 describes the synthesis of a compound of formula (71).

A² is (un)substituted heteroaryl, (un)substituted fusedheterocyclylheteroaryl, or (un)substituted fused cycloalkylheteroaryl.

R¹⁰⁰ is a substituent such as, but not limited to, H, (un)substitutedalkyl, (un)substituted alkenyl, (un)substituted alkynyl, (un)substituted-alkylene-aryl, (un)substituted -alkylene-cycloalkyl, and the like.

The amine (80) may, if desired, be treated with an alkyl halideR¹⁰⁰-Lg², wherein Lg² is a leaving group such as Br, I, orp-toluenesulfonate, and a base such as DBU or sodium hydride, to afford(71). Alternatively, (80) may be treated with a reagent R¹⁰²—C(O)—R¹⁰³wherein R¹⁰² and R¹⁰³, independently of each other, are substituentssuch as, but not limited to, H, alkyl, alkenyl, alkynyl, -alkylene-aryl,-alkylene-cycloalkyl, and the like, in the presence of a reducing agentsuch as sodium cyanoborohydrode or sodium triacetoxyborohydride, toafford (71) wherein R¹⁰⁰ should be understood as R¹⁰²—C(H)(R¹⁰³)—.

Alternatively, (78) may be treated with a reagent such as R¹⁰²C(O)—Cland a base such as TEA, or R¹⁰²C(O)—OH in the presence of a dehydratingagent such as EDC, to afford an intermediate amide, which may be reducedwith a reagent such as DIBAL or LAH, in a solvent such as THF, at atemperature of from 0° C. to 80° C., to afford (71) wherein R¹⁰⁰ shouldbe understood as —CH₂—R¹⁰². Alternatively, (71) wherein R¹⁰⁰ is —CH₃ maybe prepared by treatment of (78) with a reagent R¹⁰²—O—C(O)—Cl, orR¹⁰²O—C(O)—O—C(O)—O—R¹⁰², in the presence of a base such as TEA oraqueous alkali, to afford an intermediate which may be reduced as aboveemploying DIBAL or LAH giving (71).

Scheme 4 describes the synthesis of a compound of formula (81).

A² is (un)substituted heteroaryl, (un)substituted fusedheterocyclylheteroaryl, or (un)substituted fused cycloalkylheteroaryl.

R¹⁰⁰ and R^(10l) are, independently of each other, substituents such asbut not limited to H, (un)substituted alkyl, (un)substituted alkenyl,(un)substituted alkynyl, (un)substituted -alkylene-aryl, (un)substituted-alkylene-cycloalkyl, and the like.

The amine (73) may be treated with the reagent chlorocarbonyl isocyanatein the presence of a base such as DIEA, in a solvent such as THF, DCE,or dioxane, at a temperature of from −60° C. to 25° C. The intermediatethus formed may be treated at a temperature of from 0° C. to 80° C. with(71) to afford (81).

Scheme 5 describes the preparation of an intermediate of formula (87).

L¹¹ is, in this instance, a group such as (un)substituted alkylene or adirect bond.

R¹⁰⁴ is a substituent such as but not limited to (un)substituted alkyl,(un)substituted aryl, (un)substituted alkenyl, (un)substituted alkynyl,(un)substituted -alkylene-aryl, (un)substituted -alkylene-cycloalkyl,and the like.

The anthranilic acid (82) may be treated with an acid chlorideR¹⁰⁴—CO—Cl in the presence of a base such as TEA or aqueous alkali toafford an amide intermediate, which may be treated with a dehydratingagent such as POCl₃ or SOCl₂ in a solvent such as DCE, at a temperatureof from 0° C. to 80° C., to afford (83). A reagent (84) derived from anactive metallating agent such as lithium or magnesium metal andG¹-L¹¹-Br or G¹-L¹¹-I may be prepared. For example, where G¹ is aryl andL¹¹ is a direct bond, G¹-L¹¹-Br may be treated with n-butyllithium in asolvent such as ether, at a temperature of from −78° C. to 0° C., toafford the reagent (84) where M¹ is Li. (84) may be treated with (83) ina solvent such as THF, at a temperature of from −78° C. to 50° C., toafford (85). The amide (85) may be treated with aqueous alkali in asolvent such as ethanol, at a temperature of from 25° C. to 100° C., toafford (86).

Scheme 6 describes an alternate synthesis of a compound of formula (88).

L¹² is, in this instance, a group such as but not limited to(un)substituted alkylene, (un)substituted cycloalkylene, or a directbond.

An amine compound (87) may be treated with an acid chloride, or otheracid halide, in the presence of boron trichloride at a temperature offrom −40° C. to 25° C., followed by treatment with gallium (III)chloride and chlorobenzene and heating at a temperature of from 50° C.to 150° C., to afford (88).

Scheme 7 describes synthesis of intermediates of formulae (91), (92),(93), (94), and (95).

L¹³ is a group such as oxygen, or may be a group broadly defined as forL¹² and L¹¹. R¹⁰⁶, R¹⁰⁷ and R¹⁰⁸ are groups such as but not limited to(un)substituted alkyl, (un)substituted -alkylene-aryl, or H.

The nitrotoluene (89) can be brominated with a reagent such asN-bromosuccinimide in carbon tetrachloride to get the bromideintermediate (90). The methyl group in (89) may also be a more elaboratealkyl group with hydrogen(s) on the carbon adjacent to A¹. The bromide(90) may be treated with sodium methanesulfinate to afford intermediate(91) and with secondary or primary amines to obtain the intermediate(92). Alternately, the R¹⁰⁶ and R¹⁰⁷ groups in the compound R¹⁰⁶R¹⁰⁷NHmay be taken together for constitute an heteroaryl or heterocyclicgroup, and treatment of (90) with such a compound in the presence of abase such as potassium tert-butoxide affords (92) where the R¹⁰⁶ andR¹⁰⁷ groups are taken together for constitute a heteroaryl orheterocyclic group. Alternately, (90) may be treated with sodiumthiolacetate, followed by hydrolysis with aqueous alkali, to afford thethiol (91). From (91), various compounds may be prepared. For example,treatment of (91) with an alkylating agent such as an alkyl bromide inthe presence of base such as sodium hydride affords (93) where L¹⁴ is Sand R¹⁰⁵ is alkyl. Oxidation of this species with a reagent such asm-chloroperbenzoic acid may afford the compound where L₁₄ is —SO₂—,Compound (92) where R¹⁰⁶ is H may be treated with a compound R¹⁰⁸SO₂Clin the presence of a base such as pyridine to form (95). Alternately,(92) where R¹⁰⁶ is H may be treated with a carboxylic acid R¹⁰⁸COOH inthe presence of a peptide coupling agent such asdicyclohexylcarbodiimide to form (94).

Scheme 8 describes synthesis of compounds of formula (97).

L¹⁶ is oxygen. G¹ and L¹⁶, in this instance, preferably contain noketone, aldehyde, or primary or secondary amine groups.

R¹⁰⁹, R¹¹⁰, and R¹¹¹ are groups such as but not limited to(un)substituted alkyl, H, or (un)substituted alkylene-aryl. R¹¹⁰ andR¹¹¹ may optionally be taken together to constitute a heterocyclic ring.

Ureas of formula (91) can be reductively aminated using aminesR¹¹⁰NHR¹¹¹ and a reagend such as sodium triacetoxyborohydride in asolvent such as 1,2-dichloroethane in the presence or absence of aceticacid to obtain compounds of formula (92).

Scheme (9) describes synthesis of compounds of formulae (100) and (101).

L¹⁷ is carbonyl or sulfonyl group.

Nitrophenylureas (98) can be reduced to aniline derivatives of formula(99). Treatment of intermediate (99) with acid chlorides or sulfonylchlorides can yield compounds of formula (100). Alkylation ofintermediate (99) using aldehydes or ketones in the presense of sodiumtriacetoxyborohydride affords (101). Alternately, (99) may be treatedwith a dialkyl halide and a base such as DIEA to afford (101) where R¹¹³and R¹¹⁴ and the nitrogen to which they are attached constitute a ring.

L¹⁹ in this instance is a group such as (un)substituted alkylene. R¹¹⁵and R¹¹⁶ are independently, groups such as (un)substituted alkyl,(un)substituted alkylene-aryl, or H. Alternately, R¹¹⁵ and R¹¹⁶ may betaken together to constitute a heterocyclic ring.

The acid (102) may be coupled with an amine R¹¹⁵NHR¹¹⁶ in the presenceof a coupling agent such as dicyclohexylcarbodiimide in a solvent suchas THF or dichloromethane to afford (103).

Scheme 11

A³ is a group such as (un)substituted heteroarylene, (un)substitutedfused heterocyclylheteroarylene, or (un)substituted fusedcycloalkylheteroarylene.

R¹¹⁷ is a group such as (un)substituted alkyl, (un)substitutedalkylene-aryl, (un)substituted aryl, or (un)substituted heteroaryl.

The compound (104) may be treated with a thiol reagent in the presenceof a base such as DIEA at temperatures of from 50° C. to 150° C. toafford the thioether (105). (105) may be oxidized with a oxidizingreagent such as m-chloroperbenzoic acid in a solvent such asdichloromethane to afford the sulfone (106). Where only one equivalentof the oxidant is employed, the sulfoxide may be obtained. Where 2 ormore equivalents of oxidant are employed, the sulfone is obtained.

Scheme 12 describes the synthesis of compounds of formula (109).

A³ is a group such as (un)substituted heteroarylene, (un)substitutedfused heterocyclylheteroarylene, or (un)substituted fusedcycloalkylheteroarylene.

L²⁰ in this instance is a group such as (un)substituted alkylene. R¹¹⁷is a group such as (un)substituted alkyl, (un)substituted alkylene-aryl,(un)substituted aryl, or (un)substituted heteroaryl. Lg₂ is a leavinggroup such as chloride, methanesulfonate, or p-toluenesulfonate.

The compound (107) where Lg₂ is methanesulfonate may be synthesized fromthe precursor where Lg₂ is hydroxyl by treatment with methanesulfonylchloride in the presence of pyridine. (107) then may be treated with athiol reagent in the presence of a base such as DIEA, potassiumtert-butoxide, or sodium hydride, to afford the displacement product(108). The thioether product (108) may be oxidized to the sulfoxide orsulfone (109) as described in Scheme 11.

Scheme 13 describes the synthesis of compounds of formula (III).

L²¹ in this instance is a group such as alkylene. R¹¹⁵ and R¹¹⁶ may havethe meaning denoted previously, or may be, independently, groups such as(un)substituted alkyl, (un)substituted alkylene-aryl, (un)substitutedaryl, H, or (un)substituted heteroaryl. A³ is a group such as(un)substituted heteroarylene, (un)substituted fusedheterocyclylheteroarylene, or (un)substituted fusedcycloalkylheteroarylene.

The acid (110) may be coupled with an amine R¹¹⁵NHR¹¹⁶ in the presenceof a coupling agent such as dicyclohexylcarbodiimide to afford (111).

Scheme 14 describes a synthesis of intermediates of formula (113).

R¹¹⁸ and R¹¹⁹ may be, independently, groups such as (un)substitutedalkyl, (un)substituted alkylene-aryl, (un)substituted aryl, H, or(un)substituted heteroaryl.

Thiourea may be condensed with the bromo carbonyl compound (112) in thepresence or absence of a mild base such as potassium carbonate ortriethylamine, in a solvent such as ethanol, at a temperature of from25° C. to 120° C., to afford (113). The bromo compound (112) may beaccessed by a variety of methods known in art. For example, brominationof the ketone with pyrrolidinium hydrotribromide in THF orN-bromosuccinimide in THF in the presence of a mild base such aspotassium carbonate affords (112).

Scheme 15 describes synthesis of intermediates of formula (117)

Scheme 15 shows the synthetic route to diamides of the type (117), whereA¹, L¹, R²⁰, R¹, G¹, G² are as defined in Formula (I). Amine (114) canbe coupled with an activated oxalic or malonic esters using EDC/HOBt togive amide (115). Deprotection of the t-butyl ester of B is done withlithium hydroxide to give the carboxylic acid (116), which can becoupled using standard amide coupling reagents (eg. PyBOP) to givediamides of the type (115).

The intermediates in the above Schemes may be substituted with amino,hydroxyl, or carboxyl groups which may require protection anddeprotection during the course of preparation of Example compounds.

“Amino protection” refers to substituents of the amino group commonlyemployed to block or protect the amino functionality while reactingother functional groups on the compound. Examples of suchamino-protecting groups include the formyl group, the trityl group, thephthalimido group, the trichloroacetyl group, the chloroacetyl,bromoacetyl and iodoacetyl groups, urethane-type blocking groups such asbenzyloxycarbonyl, 4-phenylbenzyloxycarbonyl, 2-methylbenzyloxycarbonyl,4-methoxybenzyloxycarbonyl, 4-fluorobenzyloxycarbonyl,4-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl,2-chlorobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl,4-bromobenzyloxycarbonyl, 3-bromobenzyloxycarbonyl,4-nitrobenzyloxycarbonyl, 4-cyanobenzyloxy-carbonyl,2-(4-xenyl)iso-propoxycarbonyl, 1,1-diphenyleth-1-yloxycarbonyl,1,1-diphenylprop-1-yloxycarbonyl, 2-phenylprop-2-yloxycarbonyl,2-(p-toluoyl)prop-2-yloxycarbonyl, cyclopentanyloxycarbonyl,1-methylcyclopentanyloxycarbonyl, cyclohexanyloxycarbonyl,1-methylcyclohexanyloxycarbonyl, 2-methylcyclohexanyloxycarbonyl,2-(4-toluoylsulfonyl)ethoxycarbonyl, 2(methylsulfonyl)ethoxycarbonyl,2-(triphenylphosphino)ethoxycarbonyl, 9-fluorenylmethoxycarbonyl(“FMOC”), t-butoxycarbonyl (“BOC”), 2-(trimethylsilyl)ethoxycarbonyl,allyloxycarbonyl, 1-(trimethylsilylmethyl)prop-1-enyloxycarbonyl,5-benzisoxalylmethoxycarbonyl, 4-acetoxybenzyloxycarbonyl,2,2,2-trichloroethoxycarbonyl, 2-ethynyl-2-propoxycarbonyl,cyclopropylmethoxycarbonyl, 4-(decyloxy)benzyloxycarbonyl,isobornyloxycarbonyl, 1-piperidyloxycarbonyl and the like; thebenzoylmethylsulfonyl group, the 2-(nitro)phenylsulfenyl group, thediphenylphosphine oxide group and like amino-protecting groups. Thespecies of amino-protecting group employed is not critical so long asthe derivatized amino group is stable to the condition of subsequentreaction(s) on other positions of the compound of Formula (I) and can beremoved at the desired point without disrupting the remainder of themolecule. Preferred amino-protecting groups are the allyloxycarbonyl,the t-butoxycarbonyl, 9-fluorenylmethoxycarbonyl, and the trityl groups.Similar amino-protecting groups used in the cephalosporin, penicillinand peptide art are also embraced by the above terms. Further examplesof groups referred to by the above terms are described by J. W. Barton,“Protective Groups In Organic Chemistry”, J. G. W. McOmie, Ed., PlenumPress, New York, N.Y., 1973, and T. W. Greene, “Protective Groups inOrganic Synthesis”, John Wiley and Sons, New York, N.Y., 1981. Therelated term “protected amino” defines an amino group substituted withan amino-protecting group discussed above.

“Hydroxyl protection” refers to substituents of the alcohol groupcommonly employed to block or protect the alcohol functionality whilereacting other functional groups on the compound. Examples of suchalcohol-protecting groups include the 2-tetrahydropyranyl group,2-ethoxyethyl group, the trityl group, the trichloroacetyl group,urethane-type blocking groups such as benzyloxycarbonyl, and thetrialkylsilyl group, examples of such being trimethylsilyl,tert-butyldimethylsilyl, phenyldimethylsilyl, triiospropylsilyl andthexyldimethylsilyl. The choice of alcohol-protecting group employed isnot critical so long as the derivatized alcohol group is stable to thecondition of subsequent reaction(s) on other positions of the compoundof the formulae and can be removed at the desired point withoutdisrupting the remainder of the molecule. Further examples of groupsreferred to by the above terms are described by J. W. Barton,“Protective Groups In Organic Chemistry”, J. G. W. McOmie, Ed., PlenumPress, New York, N.Y., 1973, and T. W. Greene, “Protective Groups inOrganic Synthesis”, John Wiley and Sons, New York, N.Y., 1981. Therelated term “protected hydroxyl” or “protected alcohol” defines ahydroxyl group substituted with a hydroxyl-protecting group as discussedabove.

“Carboxyl protection” refers to substituents of the carboxyl groupcommonly employed to block or protect the —OH functionality whilereacting other functional groups on the compound. Examples of suchalcohol-protecting groups include the 2-tetrahydropyranyl group,2-ethoxyethyl group, the trityl group, the allyl group, thetrimethylsilylethoxymethyl group, the 2,2,2-trichloroethyl group, thebenzyl group, and the trialkylsilyl group, examples of such beingtrimethylsilyl, tert-butyldimethylsilyl, phenyldimethylsilyl,triiospropylsilyl and thexyldimethylsilyl. The choice of carboxylprotecting group employed is not critical so long as the derivatizedalcohol group is stable to the condition of subsequent reaction(s) onother positions of the compound of the formulae and can be removed atthe desired point without disrupting the remainder of the molecule.Further examples of groups referred to by the above terms are describedby J. W. Barton, “Protective Groups In Organic Chemistry”, J. G. W.McOmie, Ed., Plenum Press, New York, N.Y., 1973, and T. W. Greene,“Protective Groups in Organic Synthesis”, John Wiley and Sons, New York,N.Y., 1981. The related term “protected carboxyl” defines a carboxylgroup substituted with a carboxyl-protecting group as discussed above.

EXAMPLES General Procedure A: Preparation of 1-Aryloxy-2-nitrobenzenes,1-Arylsulfanyl-2-nitrobenzenes and 2-Aryloxy-3-nitropyridines

To a solution of potassium t-butoxide (0.62 g, 5.5 mmol) in anhydrousDMF (10 ml) was added a phenol, arylmercaptan or 2-mercaptopyridine (5.5mmol) at room temperature and the mixture was stirred for 30 min. A1-fluoro-2-nitrobenzene derivative or 2-bromo-3-nitropyridine (5.0 mmol)was added and the contents were heated at 80° C. for 12 h. The contentswere poured into water and extracted with ethyl acetate. The organiclayer was washed (dil. NaOH, water, brine), dried (Na₂SO₄) andconcentrated. In general, the desired products were of >90% pure andwere used as such for further manipulations.

General Procedure B: Preparation of 2-Aryloxyanilines,2-Arylsulfanylanilines and 3-amino-2-aryloxypyridines

The crude 2-substituted-1-nitrobenzene from procedure A was dissolved inethanol (10 ml). To this solution were added anhydrous tin(II) chloride(3.8 g, 20 mmol) and conc HCl (0.2 ml). The resulting mixture was heatedat 80° C. for 10 h, cooled and concentrated. The residue was dilutedwith water (100 ml), neutralized to pH 8-9. To the suspension, ethylacetate (40 ml) was added, stirred for 5 min and filtered throughcelite. The layers were separated and the aqueous layer was extractedwith ethyl acetate (2×10 ml). The combined organic layer was washed withbrine, dried (Na₂SO₄) and concentrated under reduced pressure to obtainthe desired aniline in 60-70% yield. In general, the desired anilineswere of >85% pure (LC-MS) and were used as such for furthermanipulations.

General Procedure C for Preparation of 2-Aryloxyanilines and2-Arylsulfanylanilines

The crude 2-substituted-1-nitrobenzene (˜5 mmol) was dissolved inmethanol (10 ml) in a 100 ml round-bottom flask. To this solution wasadded 10% palladium on charcoal (300 mg) and the flask was evacuated.The flask was filled with hydrogen with the aid of a balloon and thecontents were stirred overnight. The mixture was filtered through celiteand concentrated to obtain desired aniline (>90% purity by LC-MS).

General Procedure D: Preparation of Urea

A mixture of 1,1′-carbonyldiimidazole (98 mg, 0.6 mmol),2-aminoheteroarene (0.6 mmol) and 4-(N,N-dimethylamino)pyridine (5 mg)in dichloroethane (5 ml) was heated at 80° C. for 2 h. The reactionmixture was cooled to room temperature and was added solution of asubstituted aniline (0.5 mmol) in dichloroethane (2 ml). The resultingsuspension was heated at 80° C. for 10 h and concentrated. The residuewas purified by column chromatography (silica, CH₂Cl₂ then 10-30% ethylacetate in CH₂Cl₂) to afford the desired urea in 60-80% yield.

General Procedure E: Preparation of Urea

A mixture of isocyanate (0.5 mmol) and 2-aminoheteroarene (0.5 mmol) indichloroethane (4 ml) was heated at 80° C. for 12 h. The reactionmixture was concentrated under reduced pressure. The residue waspurified by column chromatography (silica, CH₂Cl₂ then 10-30% ethylacetate in CH₂Cl₂) to afford the desired urea in 60-80% yield.

General Procedure F: for Preparation of 2-Aryloxy-1-nitrobenzenes

To a solution of potassium t-butoxide (0.62 g, 5.5 mmol) in anhydrousTHF (20 ml) was added a phenol (5.5 mmol) at −10° C. and the mixture wasstirred for 30 min. A fluoro-1-nitrobenzene derivative (5.0 mmol) wasadded at −10° C. and stirred for 12 h at room temperature. The contentswere poured into water (25 ml) and extracted with ethyl acetate (3×20ml). The organic layer was washed (dil. NaOH, water, brine), dried(Na₂SO₄) and concentrated to give the desired products with >90% purityby LC-MS and were used as such in the next step.

General Procedure G: for Preparation of 1-Alkoxy-2-nitrobenzenes

To a suspension of NaH (60%, 0.20 g, 5.0 mmol) in anhydrous THF (10 ml)was added an alcohol (5.0 mmol) dropwise at room temperature and themixture was stirred for 30 min. 1-Fluoro-2-nitrobenzene (5.0 mmol) wasadded and the contents were heated at 60° C. for 12 h. The contents werepoured into water and extracted with ethyl acetate. The organic layerwas washed (dil. NaOH, water, brine), dried (Na₂SO₄) and concentrated.In general, the desired products were of >90% pure and were used as suchin the further manipulations.

General Procedure H: General Procedure for Preparation of Compounds ofGeneral Formula I that Contain a Urea Moiety in the Central Core

One equivalent of a mono- di- or tri.substituted aniline is dissolved inan organic solvent such as ethyl acetate, toluene, or dichloromethaneand hydrochloride dissolved in an organic solvent such as ethyl acetate,toluene or dichloromethane is added. The mixture is concentrated invacuo to give the hydrochloride of the aniline. The residue is dissolvedor suspended in a non protic organic solvent such as toluene ordichloromethane and excess (e.g. 2 to 5 equivalents) of diphosgene oranother phosgene equivalent is added. The mixture is either run at roomtemperature or heated (up to reflux temperature of the solvent) for 5 to20 hours. The reaction mixture is concentrated in vacuo and theintermediate residue used in the next step without further purification.

The crude intermediate isocyanate is dissolved in an organic solventsuch as ethyl acetate, toluene, dichloromethane, dioxane, DMSO or DMFand one equivalent of a heterocyclic amine is added. The reactionmixture is run at either room temperature or heated until the reactionis taking place. The reaction temperature will depend on the reactivityof the isocyanate and the nucleophilicity of the amine and can befollowed either using HPLC or TLC. The reaction mixture is diluted withan organic solvent such as ethyl acetate, toluene or dichloromethane andthe mixture extracted with water. The product is purified using standardprocedures as described in the art or as exemplified below.

General Procedure H1: Preparation of Amides from Carboxylic AcidsPrepared Using Procedure H

One equivalent of a N-substituted aminothiazol-4-ylcarboxylic acid orN-substituted aminothiazol-4-ylacetic acid prepared by using generalprocedure H is dissolved in an organic solvent such as1,2-dichloropropane, dimethylformamide or a mixture of two organicsolvents such as a mixture of 1,2-dichloropropane and dimethylformamide.One equivalent of PyBOP(benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphoniumhexafluorophosphate) is added, the reaction mixture is left standing for20 minutes followed by addition of two equivalents of an appropriateamine and DIPEA (diisopropylethylamine), and the mixture is leftovernight.

The reaction mixture is diluted with ethylacetate and extracted using ageneral washing procedure such as washing twice with water, twice with4N HCl, once with water, twice with 50% saturatedsodiumhydrogencarbonate, and three times with water. The organic solventis evaporated in vacuo giving an amorphous product. The product ispurified by either recrystallization in an organic solvent such asdiethylether or by HPLC (e.g. a Waters Deltprep 4000).

In case the isolated product contains a carboxylic acid esterfunctionality, the ester group can be hydrolysed to the correspondingacid by dissolving the compound in ethanol 96% and adding 2N NaOH. Themixture is left standing for some time (e.g. 2 hours) whereafter theethanol is evaporated in vacuo, water is added, and pH is adjusted toacidic with 2N HCl. The mixture is extracted with an organic solventsuch as ethylacetate and the combined organic phases are evaporated invacuo giving an amorphous product.

General Procedure H2: Preparation of Intermediate Isocyanates2-Benzylphenyl isocyanate

2-Benzylaniline (2.0 g, 11 mmol) was dissolved in ethylacetate (5 ml)and hydrochloride in ethylacetate (3N, 5 ml) was added. After 2 hrs theorganic solvent was removed in vacuo giving a solid residue. Toluene (50ml) was added, then diphosgene (2.2 g, 33 mmol) and the reaction-mixturewas heated at 110° C. for 16 hours. The solvent and excess diphosgenewas removed in vacuo giving an residual oil that was used for the nextstep without further purification.

The following isocyanates were prepared using the same procedure usedfor preparation of benzylphenyl isocyanate:

-   (5-Chloro-2-isocyanatophenyl)phenyl methanone-   2-(2-Methylphenoxy)phenyl isocyanate-   2-(4-Methoxyphenoxy)-5-(trifluoromethyl)phenyl isocyanate-   2-(Phenylsulfonyl)phenyl isocyanate

General Procedure I: Preparation of 2-acyl anilines

A solution of 1 M borontrichloride in dichloromethane (110 mL, 0.11 mol)was cooled to −20° C. To this solution was added a solution of aniline(0.1 mol) in dichloromethane (100 mL). The mixture was warmed to roomtemperature and was stirred for 3 h. The mixture was re-cooled to −20°C. Alkyl nitrile (0.1 mol) was added over 5 min, followed by 1 Msolution of (anhydrous) GaCl₃ (100 mL, 0.1 mol) in dichloromethane. Tothis solution was added chlorobenzene (300 mL) and the mixture washeated to reflux for 24 h. After being cooled to room temperature, themixture was poured into ice water (1 L) and the mixture was stirred for3 h. The organic layer was separated and the aqueous layer was extractedwith dichloromethane (4×400 mL). The combined organic layer was washedwith water (4×500 mL), brine (2×500 mL), dried over anhydrous Na₂SO₄.The aqueous layer was then basified to pH 7.5 with Na₂CO₃ and themixture was extracted with dichloromethane (2×400 mL). The organic layerwas washed with water (4×500 mL), brine (2×500 mL), dried over anhydrousNa₂SO₄. Both organic layers were combined and concentrated in vacuo. Thecrude mixture was purified by column chromatography with hexanes-ethylacetate (9:1) as eluent to give the 2-amino-alkylphenones in 10-50%yield.

General Procedure J: Preparation of Acids from Esters

The ester (1 mmol) was dissolved in 1:1 mixture of THF and methanol (5mL). To this solution was added 2 M solution of LiOH (2 mL, 4 mmol). Themixture was stirred for 1 h and was concentrated. The residue wasdiluted with water (10 mL) and the aqueous layer was washed with ether(2×10 mL). The water layer was acidified with HCl to pH 6.0 andprecipitated acid was extracted with ethyl acetate (2×50 mL). Theorganic layer was washed with water (2×20 mL), dried (Na₂SO₄) andconcentrated in vacuo to furnish the desired acid in almost quantitativeyield.

General Procedure K: Preparation of Amides

A mixture of acid (0.5 mmol) and HBTU (0.5 mmol) was dissolved inanhydrous DMF (2 mL). To this solution was added DIEA (0.6 mmol) andstirred for 2-3 minutes. A solution of alkyl amine (0.5 mmol) in DMF (1mL) was added and the mixture was stirred at room temperature for 30min. The mixture was poured into water (20 mL) and was extracted withethyl acetate (2×20 mL). The organic layer was washed with saturatedsolution of citric acid (5 mL), NaHCO3 (2×10 mL) water (2×0 mL), brine(2×10 mL), dried (Na₂SO₄) and concentrated in vacuo to give the desiredamide. The crude mixture was purified by column chromatography (silica,CH₂Cl₂ then 10-50% ethyl acetate in CH₂Cl₂) to furnish amide in 50-75%yield.

General Procedure L: Preparation of Sulfonamides/Amides

To a solution of acid (1.0 mmol) and DIEA (1.5 mmol) in anhydrous THF(20 mL) was added diphenylphosphoroyl azide (1.5 mmol) and was heated toreflux for 8-12 hours. The reaction mixture was then concentrated invacuo to give crude isocyanate. To this crude product was added diluteHCl (1.2 M, 20 mL) and the mixture was heated to reflux for 2 hours. Thereaction mixture was neutralized with Na₂CO₃ and the aqueous layer wasextracted with ethyl acetate (3×30 mL). The organic layer was washedwith water (2×30 mL), brine (1×30 mL) and dried (anhydrous Na₂SO₄) andconcentrated in vacuo to give the desired amine. This crude amine (1.0mmol) was reacted with aryl/alkylsulfonyl chloride (1 mmol) and Et₃N (2mmol) to give the desired sulfonamides. The amides were prepared asdescribed in procedure K. The crude product was purified by silica gelchromatography [hexanes:EtOAc/MeOH (70:30:0 to 5:90:5)] to furnish thedesired sulfonamides in 20-30% yield.

General Procedure M: Preparation of bis-ureas or carbamates

A mixture of acid (1.0 mmol) and DIEA (1.5 mmol) was dissolved inanhydrous THF or CH₃CN (30 mL). Then dipenylphosphoroyl azide (1.5 mmol)added to the reaction mixture. Reaction mixture was refluxed for 8-12hours. The reaction mixture was then concentrated in vacuo to give crudeisocyanate. To this crude product desired amines or alcohols (2.0 mmol)were added and stirred at rt for 2 h. The reaction mixture was thenconcentrated in vacuo. The crude reaction mixture was then purified bysilica gel chromatography (hexanes:EtOAc 70:30 to 10:90) to furnish thedesired bis-ureas or carbamates in 30-45% yield.

General Procedure N: Preparation of Alcohols

To a solution of ethyl-2-amino-4-thiazolyl acetate orethyl-2-amino-4thiazoyl carboxylate (100 mmol) in anhydrous THF (100 mL)was added lithiumborohydride (200 mmol, 2.0 M solution in THF) at −10°C., and the mixture was allowed to warm up to ambient temperature andstirred for 8-10 h. The mixture was then concentrated in vacuo. Methanol(200 mL) was added to quench excess lithiumborohydride and filteredthrough with a plug of silica gel to afford the amino alcohol.

To this crude amino alcohol (100 mmol) and imidazole (500 mmol) inanhydrous DMF (50 ml) was added tert-butyldimethylsilyl chloride (500mmol) and stirred at rt for 6 h. The reaction mixture was then washedwith water (5×100 mL) and brine (2×100 mL) and extracted withethylacetate (3×200 mL), dried over Na₂SO₄, and concentrated in vacuo togive TBS-protected amino alcohol.

TBS-protected amino alcohol (50 mmol) was subjected to urea formationfollowing general procedure D to give desired urea. This crude urea (25mmol) was then treated with TBAF (50 mmol, 1.0 M solution in THF) andstirred at rt for 4 h. The reaction mixture was poured in to water andextracted with ethyl acetate. The organic extracts were combined, washed(water), dried (Na₂SO₄) and concentrated in vacuo. The crude mixture waspurified by silica gel chromatography [hexanes:EtOAc (70:30 to 10:90)]to afford the desired alcohol in 70-80% yield.

General Procedure O: Preparation of Amines by Reductive Amination

To the aldehyde (0.11 mmol) in dichloroethane or THF (5 mL) was addedthe respective amine (0.11 mmol) and stirred at room temperature for 15min. To this solution was added sodium triacetoxyborohydride (0.16mmol). After stirring at room temperature overnight, the mixture wasconcentrated in vacuo and purified by column chromatography (silica,2-8% MeOH in DCM) to obtain the desired product in 30-50% yield.

General Procedure P: Preparation of Arylethers by Mitsunobu Reaction

To a solution of1-[2-(cyclopentanecarbonyl-4-methyl-phenyl]-3-[4-(2-hydroxy-ethyl)-thiazol-2-yl]-urea(0.268 mmol), phenol (0.536 mmol) and triphenylphosphine (0.268 mmol) inTHF (2 mL) was added diisopropyl azodicarboxylate (0.268 mmol) at 0° C.The resulting solution was stirred at rt overnight, The mixture wasconcentrated and purified by flash chromatography on silica gel (10-50%EtOAc/hexane) to give the desired product in 28-40% yield.

General procedure Q: Synthesis of1-(2-cyclopentanoyl-4-methyl-phenyl)-3-(5-alkylthio-2-thiazolyl)ureas

A mixture of1-(2-cyclopentanoyl-4-methyl-phenyl)-3-(5-bromol-2-thiazolyl)urea (1mmol), alkylthiol (2 mmol) and DIEA (2 mmol) in DMF (5 mL) was heated at80° C. for 3 h. The mixture was poured into water (20 mL) and wasextracted with ethyl acetate (3×25 mL). The organic layer was washedwith water (2×30 mL), brine (1×30 mL), dried (anhydrous Na₂SO₄) andconcentrated in vacuo to furnish a residue containing1-(2-cyclopentanoyl-4-methyl-phenyl)-3-(5-alkylthio-2-thiazolyl)ureaalong with 1-(2-cyclopentanoyl-4-methyl-phenyl)-3-(thiazol-2-yl)urea.The crude product was purified by column chromatography (silica, CH₂Cl₂then 5-20% ethyl acetate in CH₂Cl₂) to afford the desired product in25-35% yield Same procedure was adopted for the synthesis of1-(2-cyclopentanoyl-4-methyl-phenyl)-3-(5-arylthio-2-thiazolyl)ureas.The crude products were purified by column chromatography (silica,CH₂Cl₂ then 5-20% ethyl acetate in CH₂Cl₂ and 2% MeOH in CH₂Cl₂) toafford the desired product in 25-35% yield.

General Procedure R: Oxidation of Alkyl and Arylthio SubstitutedThiazolyl Ureas

Alkyl or arylthio substituted thiazolyl urea (0.5 mmol) was dissolved inCH₂Cl₂ (5 mL) and was cooled to 0° C. in an ice bath. To this solutionwas added m-cpba (133 mg, 0.75 mmol) in CH₂Cl₂ (3 mL). The mixture wasstirred at 0° C. for 4 h and was diluted with CH₂Cl₂ (30 mL). Theorganic layer was washed with saturated solution of NaHCO₃ (2×20 mL),water (3×20 mL), brine (1×20 mL), dried (anhydrous Na₂SO₄) andconcentrated in vacuo. The crude mixture was purified by columnchromatography (silica, CH₂Cl₂ then 5-20% ethyl acetate in CH₂Cl₂ and 2%MeOH in CH₂Cl₂) to give the desired alkyl or aryl sulfone in 60-80%yield.

General Procedure S: Preparation of 2-Amino Arylphenones

To a solution of 2-amino benzoic acid (10 mmol) in THF was added benzoylchloride (2.8 g, 20 mmol) followed by pyridine (1.58 g, 20 mmol). Themixture was stirred for 1 h at room temperature. The2-phenyl-benzo[d][1,3]oxazin-4-one formed was filtered and the residuewas washed with water and dried in vacuum desiccator.

To a solution of 2-phenyl-benzo[d][1,3]oxazin-4-one (5 mmol) in dryCH₂Cl₂ (20 mL) was added 1N solution of aryl magnesium bromide in THF (5mL) at 0° C. The mixture was stirred at room temperature for 2 h andpoured into water (30 mL). The aqueous layer was extracted with ethylacetate (3×30 mL) and was washed with water (3×50 mL), brine (1×50 mL),dried (anhydrous Na₂SO₄) and concentrated in vacuo to affordN-(2-benzoyl-phenyl)-benzamide in 60-70% yield.

To a solution of the crude N-(2-benzoyl-phenyl)-benzamide (2 mmol) inTHF (10 mL) was added 10 N solution of NaOH (5 mL) and was heated toreflux for 18 h. The mixture was poured into water (50 mL) and wasextracted with ethyl acetate (3×30 mL). The organic layer was washedwith water (3×50 mL), brine (1×50 mL), dried (anhydrous Na₂SO₄) andconcentrated in vacuo to afford 2-amino arylphenone. The crude productwas purified by column chromatography (silica, hexanes then 5-20% ethylacetate) to furnish the desired product in 28-40% yield.

General Procedure T: Preparation of Amides/Sulfonamides

To a solution of amine (0.5 mmol) in DCM (5 mL) was added triethylamine(1 mmol) and cooled the reaction mixture to 0° C. Acid chloride orsulfonyl chloride (0.5 mmol) was added drop-wise and stirred forovernight. The reaction mixture was concentrated in vacuo and theresidue was purified by column chromatography [silica, DCM:ethyl acetate(80:20 to 20:80)] to yield desired amides or sulfonamides respectively.

General Procedure U: Preparation of Hydantoins from Amino Acids

To a solution of Boc-Gly-Merrifield resin (1.2 g, 0.96 mmol) was addedtrifluoroacetic acid (5 ml, 20% in DCM), then the resin was washed withthree cycles of DMF, methanol, and DCM. To this resin in DCM (20 mL) wasslowly added phosgene (1.0 mL, 20% in toluene, 2.0 mmol)) andtriethylamine (0.56 ml, 4.0 mmol) at −20° C. The reaction mixture wasallowed to warm up to room temperature. The excess phosgene was washedaway with there cycles of DCM. To this resin in DCM (20 mL) was added1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(0.9 g, 2.5 mmol) in DCM (10 mL) and the reaction mixture was placed ina shaker and reacted for 4 h to give the corresponding urea. The resinwas then washed with three cycles of DMF, methanol and DCM and driedover 2 h. To the resin was added triethylamine (10 mL, 20% solution inTHF) and the reaction mixture was heated for 16 h. The mixture wasfiltered and the filtrate was concentrated in vacuo to afford hydantoinsin 60-75% overall yields.

General Procedure V: Preparation of Specific 2-Aminothiazole Analogs

To a solution of 1,3-dichloroacetone, 1,3-dibromoacetone,1-acetoxy-3-chloroacetone, bromomalonaldehyde or1,4-dibromobutan-2,3-dione (100 mmol) in methanol (100 ml) was addedthiourea (7.6 g, 100 mmol) and the mixture was stirred at rt. for 3 h.The reaction mixture was concentrated in vacuo to give the desiredproducts in almost quantitative yields.

4-Chloromethyl-thiazole-2-ylamine (172 mg, 1.0 mmol) was reacted witharylthiols (2 mmol) and DIEA (2 mmol) in THF (5 mL) following thegeneral procedure Z. These intermediates were coupled with CDI and2-amino-5-methyl-phenyl)-cyclopentyl-methanone (203 mg, 1.0 mmol)following the general procedure D.

General Procedure W: Preparation of alkylamino nitrobenzenes

1-Fluoro-2-nitrobenzene derivative (5.0 mmol) and an amine (10 mmol) inTHF (25 mL) were heated at 60° C. for 12 h. The contents were pouredinto water and extracted with ethyl acetate. The organic layer waswashed (water, brine), dried (Na₂SO₄) and concentrated. The residue wasdissolved in methanol (25 mL) and subjected reduction following thegeneral procedure C. In general, the desired products were of >90% pureand were used as such in the further manipulations.

General Procedure X: Preparation of Alkenes by Wittig Reaction

The aldehyde (0.10 g, 0.28 mmol) and(carbethoxymethylene)-triphenylphosphorane (0.12 g, 0.34 mmol) werestirred at room temperature in benzene overnight. The reaction mixturewas concentrated under vacuum and purified by column chromatography(silica, 15% EtOAc/hexanes) to obtain the product in 80% yield.

General procedure Y: Synthesis of1-(2-cyclopentanoyl-4-methyl-phenyl)-3-(5-arylthio-2-thiazolyl)ureas

A mixture of1-(2-cyclopentanoyl-4-methyl-phenyl)-3-(5-bromol-2-thiazolyl)urea (1mmol), arylthiol (2 mmol) and tert. BuOK (2 mmol; 4 equivalent oftert.BuOK was used for arylthio carboxylic acids) in DMF (5 mL) washeated at 80° C. for 3 h. The mixture was poured into water (20 mL).Urea containing arylthio carboxylic acid was neutralized with saturatedNaHCO₃ solution. The aqueous layer was extracted with ethyl acetate(3×25 mL). The organic layer was washed with water (2×30 mL), brine(1×30 mL), dried (anhydrous Na₂SO₄) and concentrated in vacuo to furnisha residue containing1-(2-cyclopentanoyl-4-methyl-phenyl)-3-(5-arylthio-2-thiazolyl)ureaalong with 1-(2-cyclopentanoyl-4-methyl-phenyl)-3-(2-thiazolyl)urea. Thecrude product was purified by column chromatography (silica, CH₂Cl₂ then5-20% ethyl acetate in CH₂Cl₂ and 2% MeOH in CH₂Cl₂) to afford thedesired product in 25-35% yield.

General procedure Z: Synthesis of1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(aryl-sulfanylmethyl)-thiazol-2-yl]-ureasand1-(2-cyclopentanecarbonyl-4-methyl-Phenyl)-3-{4-[arylsulfanyl)-ethyl]-thiazol-2-yl}-ureas

A mixture of1-(4-chloromethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(1 mmol), arylthiol (2 mmol) and DIEA (2 mmol) in THF (5 mL) was heatedat 80° C. for 3 h. The mixture was poured into water (20 mL) and wasextracted with ethyl acetate (3×25 mL). The organic layer was washedwith water (2×30 mL), brine (1×30 mL), dried (anhydrous Na₂SO₄) andconcentrated in vacuo to furnish a residue containing1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(arylsulfanylmethyl)-thiazol-2-yl]-urea.The crude product was purified by column chromatography (silica, CH₂Cl₂then 5-20% ethyl acetate in CH₂Cl₂ and 2% MeOH in CH₂Cl₂) to afford thedesired product in 79-85% yield

Similarly, synthesis of1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[arylsulfanyl)-ethyl]-thiazol-2-yl}-ureawas carried out by reacting methanesulfonic acid2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethylester with arylthiol and Et₃N. This afforded the desired product in60-80% yield.

General Procedure AA: Preparation of Urea

A mixture of 1,1′-carbonyldiimidazole (98 mg, 0.6 mmol),(2-aminothiazol-4-yl)acetic acid ethyl ester (0.6 mmol) and4-(N,N-dimethylamino)pyridine (2 mg) in dichloromethane (5 ml) wasstirred at room temperature for 2 h. A solution of a substituted anilinederivative (0.6 mmol) in dichloromethane (1 ml) was added and stirringwas continued at room temperature for 24 h. The reaction mixture wasconcentrated and the residue was purified by column chromatography(silica, CH₂Cl₂ then 10-30% ethyl acetate in CH₂Cl₂) to afford thedesired urea.

HPLC-MS (Method A)

The following instrumentation is used:

-   -   Hewlett Packard series 1100 G1312A Bin Pump    -   Hewlett Packard series 1100 Column compartment    -   Hewlett Packard series 1100 G1315A DAD diode array detector    -   Hewlett Packard series 1100 MSD    -   Sedere 75 Evaporative Light Scattering detector

The instrument is controlled by HP Chemstation software.

The HPLC pump is connected to two eluent reservoirs containing:

-   -   A: 0.01% TFA in water    -   B: 0.01% TFA in acetonitrile

The analysis is performed at 40° C. by injecting an appropriate volumeof the sample (preferably 1 μl) onto the column which is eluted with agradient of acetonitrile.

The HPLC conditions, detector settings and mass spectrometer settingsused are giving in the following table.

-   -   Column: Waters Xterra MS C-18×3 mm id 5 □m    -   Gradient: 5%-100% acetonitrile linear during 7.5 min at 1.5        ml/min    -   Detection: 210 nm (analogue output from DAD (diode array        detector))    -   ELS (analogue output from ELS)    -   MS ionisation mode API-ES    -   Scan 100-1000 amu step 0.1 amu

After the DAD the flow is divided yielding approx 1 ml/min to the ELSand 0.5 ml/min to the MS.

Example 1 N-(2-Phenoxyphenyl)-N′-(thiazol-2-yl)urea

N-(2-Phenoxyphenyl)-N′-(thiazol-2-yl)urea (0.59 g, 94.9%) was preparedfrom 2-phenoxyaniline (0.37 g, 2.00 mmol) and 2-aminothiazole (0.20 g,2.00 mmol) following the general procedure D.

LC-MS (m/z): 313 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.76 (d, J=13.8 Hz, 1H), 6.98-7.04 (m,4H), 7.11 (t, J=4.8 Hz, 2H), 7.32 (t, J=8.0 Hz, 2H), and 8.35 (dd,J=1.6, 8.0 Hz, 1H), 10.2 (br, 2H).

Example 2N-[2-(2,3-Dimethoxyphenoxy)-5-Fluorophenyl]-N′-(thizol-2-yl)sulfamide

To a solution of sulfuryl chloride (2.0 ml, 2.0 mmol, 1.0 M solution indichloro-methane) were added p-nitrophenol (0.55 g, 4.0 mmol) indichloromethane and N,N-diisopropylethylamine (0.71 ml, 4.0 mmol) at−78° C. The reaction mixture was stirred for 1 hour at −78° C. and2-(2,3-dimethoxyphenoxy)-5-fluoroaniline (0.52 g, 2.0 mmol) indichloromethane (5 ml) was added. The reaction mixture was stirred for10 min and 2-aminothiazole (0.2 g, 2.0 mmol) was added. The reactionmixture was allowed to warm up slowly to ambient temperature. Themixture was concentrated under reduced pressure. The residue wasdissolved in ethyl acetate and was washed (dil. NaOH, water, brine),dried (Na₂SO₄) and concentrated under reduced pressure. The crudeproduct was treated with Dowex-50 acidic resin in ethyl acetate-methanol(1:1) to remove unreacted 2-aminothiazole. The filtrate was concentratedand the residue was purified by silica gel column chromatography(ethylacetate:hexanes, from 50:50 to 90:10 as eluent system) to affordthe title compound (0.42 g, 49%).

LC-MS (m/z): 427 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.12 (br, 2H), 3.71 (s, 3H), 3.86 (s,3H), 6.56 (dd, J=7.6, 1.6 Hz, 1H), 6.66 (m, 1H), 6.77-6.87 (m, 3H), 6.99(t, J=3.6 Hz, 1H), 7.26 (d, J=4.8 Hz, 1H), and 7.38 (dd, J=10.8, 3.2 Hz,1H)

Example 3 1-(2-phenoxyphenyl)-5-(thiazol-2-yl)biuret

To a solution of 2-phenoxyaniline (0.46 g, 2.50 mmol) in tetrahydrofuran(20 ml) was added diisopropylethylamine (0.89 ml, 5.00 mmol) and thesolution was cooled to −30° C., then N-(chlorocarbonyl)isocyanate (0.3ml, 3.75 mmol) was slowly added. The mixture was then allowed to warm upto the room temperature during 30 min. 2-Aminothiazole (0.375 g, 3.75mmol) was added to the reaction mixture and stirred at room temperaturefor 6 hours. The reaction mixture was concentrated under reducedpressure to afford crude product, which was purified by silica gelchromatography (hexanes:ethyl acetate from 80:20 to 30:70) to affordtitle compound (0.49 g, 55%) as pale yellow solid.

LC-MS (m/z): 356 (M+1).

¹H NMR (400 MHz, acetone-d₆): δ 6.92 (dd, J=1.6, 7.6 Hz, 1H), 7.06 (m,5H), 7.40 (m, 3H), 8.32 (d, J=4.8 Hz, 1H), 8.45 (d, J=5.6 Hz, 1H), 9.02(br, 1H), 9.78 (br, 1H), and 10.46 (br, 1H).

Example 4 2-[([[(2-Phenoxyanilino)sulfonyl]amino]carbonyl)amino]thiazole

To a solution of chlorosulfonyl isocyanate (0.22 ml, 2.5 mmol) intetrahydrofuran (25 ml) were added 2-phenoxyaniline (0.37 g, 2.0 mmol)and DIEA (0.89 ml, 5.0 mmol) at −78° C. The solution was stirred andslowly allowed to warmed up to 0° C. To this reaction mixture, was added2-amino thiazole (0.20 g, 2.0 mmol) and continued stirring at roomtemperature for 3 h. The reaction mixture was concentrated under reducedpressure and the crude product was purified by column chromatography(ethylacetate:hexanes, from 50:50 to 90:10 as eluent system) to affordthe title compound (0.52 g, 66%).

LC-MS (m/z): 392 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.85 (dd, J=8.8, 1.6 Hz, 1H), 6.88 (dd,J=1.6, 8.8 Hz, 1H), 7.00-7.16 (m, 5H), 7.29-7.39 (m, 4H), 10.33 (br,1H), 10.88 (br, 2H).

Example 5 N-(2-Phenylsulfanylphenyl)-N′-(thiazol-2-yl)urea

N-(2-Phenylsulfanylphenyl)-N′-(thiazol-2-yl)urea (116 mg, 71%) wasprepared from 2-phenylsulfanylaniline (100 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 329 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 7.03 (d, J=3.6 Hz, 1H), 7.10-7.18 (m,4H), 7.25-7.31 (m, 3H), 7.48 (m, 1H), 7.59 (dd, J=3.6, 1.6 Hz, 1H), 8.44(dd, J=8.4, 1.2 Hz, 1H), 9.00 (br, 1H), 10.44 (br, 1H).

Example 6 N-(2-Phenylsulfonylphenyl)-N′-(thiazol-2-yl)urea

N-(2-Phenylsulfonylphenyl)-N′-(thiazol-2-yl)urea (98 mg, 55%) wasprepared from 2-phenylsulfonylaniline (116 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 361 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 7.07 (d, J=3.6 Hz, 1H), 7.33-7.37 (m,1H), 7.40 (d, J=3.6 Hz, 1H), 7.55-7.60 (m, 2H), 7.63-7.71 (m, 2H),7.98-8.01 (m, 2H), 8.12 (d, J=8.0 Hz, 1H), 8.22-8.25 (m, 1H), 9.26 (br,1H), 10.99 (br, 1H).

Example 7 N-(2-Benzylphenyl)-N′-(thiazol-2-yl)urea

N-(2-Benzylphenyl)-N′-(thiazol-2-yl)urea (111 mg, 72%) was prepared fromcommercially available 2-benzylaniline (91 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 311 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 4.08 (s, 2H), 7.02 (d, J=3.2 Hz, 1H),7.06-7.14 (m, 2H), 7.14-7.19 (m, 4H), 7.23-7.29 (m, 4H), 7.96 (d, J=8.4Hz, 1H), 8.75 (br, 1H), 10.01 (br, 1H).

Example 8 N-(2-Benzoylphenyl)-N′-(thiazol-2-yl)urea

N-(2-Benzoylphenyl)-N′-(thiazol-2-yl)urea (100 mg, 63%) was preparedfrom 2-aminobenzophenone (97 mg, 0.5 mmol) and 2-aminothiazole (60 mg,0.6 mmol) following the general procedure D.

LC-MS (m/z): 325 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 7.05 (s, 1H), 7.16 (s, 1H), 7.35 (d,J=3.6 Hz, 1H), 7.54 (d, J=7.2 Hz, 2H), 7.65 (s, 1H), 7.75 (s, 1H), 8.45(s, 1H), 10.18 (br, 1H), 10.85 (br, 1H).

Example 9 N-[2-(Phenylamino)phenyl]-N′-(thiazol-2-yl)urea

N-[2-(Phenylamino)phenyl]-N′-(thiazol-2-yl)urea (75 mg, 49%) wasprepared from 2-(N-Phenylamino)aniline (92 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 312 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.75-6.79 (m, 3H), 6.86 (br, 1H), 7.01(d, J=3.6 Hz, 1H), 7.05-7.09 (m, 1H), 7.15-7.19 (m, 3H), 7.24-7.28 (m,2H), 8.16 (d, J=8.0, 1.2 Hz, 1H), 8.65 (br, 1H), 10.15 (br, 1H).

Example 10 N-[2-Fluoro-6-(4-methoxyphenoxy)benzyl]-N′-(thiazol-2-yl)urea

N-[2-Fluoro-6-(4-methoxyphenoxy)benzyl]-N′-(thiazol-2-yl)urea (0.61 g,81%) was prepared from 2-fluoro-6-(4-methoxyphenoxy)benzylamine (0.494g, 2.00 mmol) and 2-aminothiazole (0.20 g, 2.00 mmol) following thegeneral procedure D.

LC-MS (m/z): 327 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.06 (br, 1H), 3.78 (s, 3H), 4.67 (d,J=4.8 Hz, 2H), 6.52 (d, J=8.4 Hz, 1H), 6.85 (t, J=9.6 Hz, 1H), 6.95 (m,3H), 7.05 (m, 2H), 7.24 (m, 2H), 10.06 (br, 1H).

Example 11 N-(2-Benzyloxyphenyl)-N′-(thiazol-2-yl)urea

N-(2-Benzyloxyphenyl)-N′-(thiazol-2-yl)urea (0.56 g, 86%) was preparedfrom 2-benzyloxyaniline (0.40 g, 2.00 mmol) and 2-aminothiazole (0.20 g,2.00 mmol) following the general procedure D.

LC-MS (m/z): 327 (M+1).

¹H NMR (400 MHz, CDCl₃): δ 4.00 (br, 2H), 5.15 (s, 2H), 6.85 (dd, J=1.6,8.8 Hz, 2H), 6.97 (dd, J=1.6, 7.2 Hz, 1H), 6.98 (dd, J=2.0, 6.0 Hz, 1H),7.37 (m, 2H), 7.46 (t, J=7.2 Hz, 1H), 7.52 (d, J=5.6 Hz, 2H), and 7.56(d, J=6.8 Hz, 2H)

Example 12 N-[2-(2,3,4-Trimethoxybenzyloxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2,3,4-Trimethoxybenzyloxy)-1-nitrobenzene (0.46 g, 72%) was preparedfrom 2,3,4-trimethoxybenzyl alcohol (0.35 ml, 2.0 mmol) and1-fluoro-2-nitrobenzene (0.21 ml, 2.0 mmol) following the generalprocedure G. This was reduced to 2-(2,3,4-trimethoxybenzyl-oxy)aniline(0.26 g, 65%) following the general procedure B.N-[2-(2,3,4-trimethoxybenzyl-oxy)phenyl]-N′-(thiazol-2-yl)urea (240 mg,65%) was prepared from 2-(2,3,4-trimethoxy-benzyloxy)aniline (0.26 g,0.9 mmol) and 2-aminothiazole (140 mg, 1.4 mmol) following the generalprocedure D.

LC-MS (m/z): 417 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.72 (s, 3H), 3.73 (s, 3H), 3.81 (s,3H), 3.88 (s, 2H), 6.73-7.36 (m, 7H), 8.15 (t, J=8.4 Hz, 1H), 8.90 (br,1H), 10.10 (br, 1H).

Example 13 N-(2-Ethoxyphenyl)-N′-(thiazol-2-yl)urea

N-(2-Ethoxyphenyl)-N′-(thiazol-2-yl)urea (95 mg, 72%) was prepared fromcommercially available 2-ethoxyaniline (68 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 265 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 1.29 (t, J=7.0 Hz, 3H), 3.94-3.98 (q,J=7.0 Hz, 2H), 6.74-6.88 (m, 4H), 7.27 (d, J=5.2 Hz, 1H), 8.17 (dd,J=1.6, 8.0 Hz, 1H), 8.42 (br, 1H), 10.92 (br, 1H).

Example 14 N-(2-Phenoxyphenyl)-N′-(pyridin-2-yl)urea

N-(2-Phenoxyphenyl)-N′-(pyridin-2-yl)urea (109 mg, 72%) was preparedfrom 2-phenoxyphenylisocyanate (106 mg, 0.5 mmol) and 2-aminopyridine(60 mg, 0.6 mmol) following the general procedure E.

LC-MS (m/z): 307 (M+1)⁺.

¹H NMR (400 MHz, DMSO-d₆): δ 6.88-6.91 (m, 1H), 6.96-7.08 (m, 4H),7.15-7.19 (m, 2H), 7.32-7.36 (m, 2H), 7.65-7.69 (m, 1H), 7.88 (d, J=4.0Hz, 1H), 8.36 (d, J=8.0 Hz, 1H), 9.84 (s, 1H), 11.5 (br, 1H).

Example 15N-(2-Phenoxyphenyl)-N′-[(4-methoxycarbonylmethyl)thiazol-2-yl]urea

N-(2-Phenoxyphenyl)-N′-[(4-methoxycarbonylmethyl)thiazol-2-yl]urea (130mg, 65%) was prepared from 2-phenoxyphenylisocyanate (106 mg, 0.5 mmol)and methyl 2-aminothiazole-4-acetate (104 mg, 0.6 mmol) following thegeneral procedure E.

LC-MS (m/z): 401 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.58 (s, 2H), 3.61 (s, 3H), 6.84-6.89(m, 2H), 7.01-7.05 (m, 3H), 7.13-7.18 (m, 2H), 7.38-8.42 (m, 2H), 8.40(d, J=8.0 Hz, 1H), 8.91 (br, 1H), 10.12 (br, 1H).

Example 16 N-Methyl-N-(2-phenoxyphenyl)-N′-(thiazol-2-yl)urea

2-Phenoxyaniline (0.93 g, 5.00 mmol) and di-tert-butyl dicarbonate (2.18g, 10.0 mmol) were dissolved in anhydrous dioxane (50 ml), then thereaction mixture was refluxed for 3 h. The mixture was concentratedunder reduced pressure to quantitatively give2-phenoxy-N-(t-butoxycarbonyl)aniline (1.43 g). The product wasconfirmed by LC-MS and subjected to next reaction without furtherpurification.

To a solution of 2-phenoxy-N-(t-butoxycarbonyl)aniline (1.43 g, 5.0mmol) in anhydrous tetrahydrofuran (50 ml) was added lithiumaluminumhydride (10 ml, 10.0 mmol, 1.0 M solution in tetrahydrofuran) at−10° C. The mixture was then refluxed at 65° C. overnight. The reactionmixture was quenched with slow addition of MeOH (10 ml) and concentratedunder reduced pressure. The reaction mixture was then poured into water(50 ml) and extracted with ethyl acetate (3×100 ml). Organic extractswere combined and washed with brine (2×100 ml) and dried over (Na₂SO₄),concentrated under reduced pressure to give N-methyl-2-phenoxyaniline(0.94 g, 94.0%) as a pale yellow oil. The product was confirmed by LC-MSand subjected to next reaction without further purification.

To a solution of 2-aminothiazole (0.20 g, 2.00 mmol) in dichloroethane(20 ml) was added 1,1′-carbonyldiimidazole (0.40 g, 2.5 mmol) andN,N-dimethylaminopyridine (0.05 g, 0.4 mmol) then the solution wasrefluxed at 80° C. for 1 h. N-Methyl-2-phenoxyaniline (0.40 g, 2.00mmol) was added to the solution. The reaction mixture was then stirredovernight at 80° C. The reaction was monitored by LC-MS and TLC, thenconcentrated under reduced pressure to afford crude product whichsubsequently was subjected to silica gel chromatography (hexanes:ethylacetate from 80:20 to 50:50 as eluent system) to afford title product(0.48 g, 73%) as orange solid.

LC-MS (m/z): 327 (M+1)⁺.

¹H NMR (400 MHz, CDCl₃): δ 3.30 (s, 3H), 6.84 (d, J=4.8 Hz, 1H), 6.97(m, 3H), 7.16 (m, 2H), 7.29 (m, 5H), and 7.74 (br, 1H).

Example 17 N-isopropyl-N-(2-phenoxyphenyl)-N′-(thiazol-2-yl)urea

To a solution of 2-phenoxyaniline (0.93 g, 5.0 mmol) in dichloroethane(50 ml) was added anhydrous acetone (0.73 ml, 10.0 mmol) and acetic acid(0.1 ml, 2.0 mmol). The mixture was stirred for 30 min, and sodiumtriacetoxyborohydride (3.18 g, 15.0 mmol) was added in one portion. Thereaction mixture was stirred overnight at ambient temperature. Thereaction mixture was quenched by slow addition of MeOH (10 ml) andconcentrated under reduced pressure. The residue was poured into water(50 ml) and extracted with ethyl acetate (3×100 ml). Organic extractswere combined and washed with brine (2×100 ml) and dried (Na₂SO₄),concentrated under reduced pressure to give N-isopropyl-2-phenoxyaniline(1.05 g, 91%) as colorless oil.

To a solution of 2-aminothiazole (0.20 g, 2.00 mmol) in dichloroethane(20 ml) was added 1,1′-carbonyldiimidazole (0.40 g, 2.5 mmol) andN,N-dimethylaminopyridine (0.05 g, 0.4 mmol) then the solution wasrefluxed at 80° C. for 1 h. N-Isopropyl-2-phenoxyaniline (0.46 g, 2.0mmol) was added and the reaction mixture was then stirred overnight at80° C. The reaction mixture was concentrated under reduced pressure toafford crude product, which was purified by silica gel chromatography(hexanes:ethyl acetate from 80:20 to 50:50 as eluent system) to affordtitle product (0.56 g, 79%).

LC-MS (m/z): 355 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 1.22 (d, J=6.4 Hz, 6H), 4.81 (m, 1H),6.91 (m, 2H), 7.10-7.24 (m, 5H), 7.39 (m, 4H), and 9.00 (br, 1H).

Example 18 N-[2-(4-Methoxyphenoxy)phenyl)-N′-(thiazol-2-yl)urea

2-(4-Methoxyphenoxy)-1-nitrobenzene (0.98 g, 80%) was prepared from4-methoxyphenol (0.62 g, 5.0 mmol) and 1-fluoro-2-nitrobenzene (0.71 g,5.0 mmol) following the general procedure A. This was reduced to2-(4-methoxyphenoxy)aniline (0.32 g, 60%, 2.5 mmol scale) following thegeneral procedure B.N-[2-(4-Methoxyphenoxy)phenyl)-N′-(thiazol-2-yl)urea (256 mg, 75%) wasprepared from 2-(4-methoxyphenoxy)aniline (215 mg, 1.0 mmol) and2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

LC-MS (m/z): 343 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.80 (s, 3H), 6.80 (d, J=8.0 Hz, 1H),6.98-7.05 (m, 6H), 7.10 (m, 1H), 7.32 (d, J=3.6 Hz, 1H), 8.40 (d, J=8.0Hz, 1H), 8.90 (br, 1H), 10.23 (br, 1H).

Example 19 N-[2-(4-Fluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(4-Fluorophenoxy)-1-nitrobenzene (0.87 g, 75%) was prepared from4-fluoro-phenol (0.62 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71 g,5.0 mmol) following the general procedure A. This was reduced to2-(4-fluorophenoxy)aniline (0.51 g, 68%) following general procedure B.N-[2-(4-Fluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea (118 mg, 72%) wasprepared from 2-(4-fluorophenoxy)aniline (102 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 331 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.89 (dd, J=8.4, 1.2 Hz, 1H), 7.01-7.11(m, 4H), 7.14-7.29 (m, 3H), 7.31 (d, J=3.6 Hz, 1H), 8.42 (dd, J=8.0, 1.6Hz, 1H), 9.12 (br, 1H), 10.19 (br, 1H).

Example 20 N-[2-(4-Chlorophenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(4-Chlorophenoxy)-1-nitrobenzene (0.88 g, 71%) was prepared from4-chlorophenol (0.70 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71 g,5.0 mmol) following the general procedure A. This was reduced to2-(4-chlorophenoxy)aniline (0.50 g, 65%) following general procedure B.N-[2-(4-Chlorophenoxy)phenyl]-N′-(thiazol-2-yl)urea (106 mg, 62%) wasprepared from 2-(4-chlorophenoxy)aniline (109 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 347 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.98 (d, J=7.6 Hz, 1H), 7.04-7.09 (m,4H), 7.19-7.23 (m, 1H), 7.31 (d, J=3.6 Hz, 1H), 7.39-7.43 (m, 2H), 8.44(dd, J=8.4, 1.6 Hz, 1H), 8.90 (br, 1H), 10.13 (br, 1H).

Example 21 N-[2-(4-Cyanophenoxy)phenyl]-N′-thiazolylurea

2-(4-Cyanophenoxy)-1-nitrobenzene (0.82 g, 69%) was prepared from4-cyano-phenol (0.66 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71 g,5.0 mmol) following the general procedure A. This was reduced to2-(4-cyanophenoxy)aniline (0.47 g, 65%) following general procedure B.N-[2-(4-Cyanophenoxy)phenyl]-N′-thiazolylurea (110 mg, 65%) was preparedfrom 2-(4-cyanophenoxy)aniline (105 mg, 0.5 mmol) and 2-aminothiazole(60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 338 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.04 (d, J=8.0 Hz, 1H), 7.13-7.18 (m,4H), 7.28-7.33 (m, 2H), 7.78-7.81 (m, 2H), 8.47 (d, J=8.0 Hz, 1H), 8.95(br, 1H), 10.43 (br, 1H).

Example 22 N-[2-(4-Methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(4-Methoxycarbonylphenoxy)-1-nitrobenzene (0.79 g, 58%) was preparedfrom methyl 4-hydroxybenzoate (0.84 g, 5.5 mmol) and1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the generalprocedure A. This was reduced to 2-(4-methoxycarbonylphenoxy)-aniline(0.46 g, 66%) following general procedure B.N-[2-(4-Methoxycarbonylphenoxy)-phenyl]-N′-(thiazol-2-yl)urea (100 mg,55%) was prepared from 2-(4-methoxycarbonyl-phenoxy)aniline (122 mg, 0.5mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 371 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.85 (s, 3H), 7.03 (d, J=3.6 Hz, 1H),7.07-7.14 (m, 4H), 7.25-7.29 (m, 2H), 8.01-4.04 (m, 2H), 8.46 (dd,J=8.1, 1.2 Hz, 1H), 8.76 (br, 1H), 10.07 (br, 1H).

Example 23 N-[2-(4-Isopropylphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(4-Isopropylphenoxy)-1-nitrobenzene (0.95 g, 75%) was prepared from4-isopropylphenol (0.68 g, 5.0 mmol) and 1-fluoro-2-nitrobenzene (0.71g, 5.0 mmol) following the general procedure A. This was reduced to2-(4-isopropylphenoxy)aniline (0.34 g, 60%, 2.5 mmol scale) followinggeneral procedure B.N-[2-(4-Isopropylphenoxy)phenyl]-N′-(thiazol-2-yl)urea (247 mg, 70%) wasprepared from 2-(4-isopropylphenoxy)aniline (227 mg, 1.0 mmol) and2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

LC-MS (m/z): 355 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 1.17 (d, J=7.2 Hz, 3H), 1.22 (d, J=6.8Hz, 3H), 2.88 (m, 1H), 6.74 (d, J=6.6 Hz, 1H), 6.88 (d, J=8.0 Hz, 1H),6.94-7.15 (m, 4H), 7.28 (m, 2H), 8.43 (d, J=8.2 Hz, 1H), 10.15 (br, 2H).

Example 24 N-[2-(3,4-Difluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(3,4-Difluorophenoxy)-1-nitrobenzene (0.76 g, 60%) was prepared from3,4-difluorophenol (0.65 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71g, 5.0 mmol) following the general procedure A. This was reduced to2-(3,4-difluorophenoxy)aniline (0.33 g, 60%, 2.5 mmol scale) followinggeneral procedure B.N-[2-(3,4-Difluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea (312 mg, 60%)was prepared from 2-(3,4-difluorophenoxy)aniline (330 mg, 1.5 mmol) and2-aminothiazole (150 mg, 1.5 mmol) following the general procedure D.

LC-MS (m/z): 349 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.88 (m, 1H), 7.01 (d, J=8.0 Hz, 1H),7.04-7.12 (m, 4H), 7.22 (m, 1H), 7.30-7.42 (m, 2H), 8.43 (d, J=8.2 Hz,1H), 10.16 (br, 2H).

Example 25 N-[2-(3,4-Dichlorophenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(3,4-Dichlorophenoxy)-1-nitrobenzene (1.15 g, 81%) was prepared from3,4-dichlorophenol (0.9 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71g, 5.0 mmol) following the general procedure A. This was reduced to2-(3,4-dichlorophenoxy)aniline (0.69 g, 68%) following general procedureB. N-[2-(3,4-Dichlorophenoxy)phenyl]-N′-(thiazol-2-yl)urea (129 mg, 68%)was prepared from 2-(3,4-dichlorophenoxy)aniline (127 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 382 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.99-7.13 (m, 4H), 7.24-7.28 (m, 2H),7.30 (d, J=3.6 Hz, 1H), 7.57 (d, J=9.2 Hz, 1H), 8.44 (dd, J=8.4, 1.2 Hz,1H), 9.20 (br, 1H), 10.09 (br, 1H).

Example 26 N-[2-(4-Chloro-3-methylphenoxy)phenyl]-N′-(thiazol-2-yl)urea

N-[2-(4-Chloro-3-methylphenoxy)phenyl]-N′-(thiazol-2-yl)urea (233 mg,65%) was prepared from 2-(4-chloro-3-methylphenoxy)aniline (233 mg, 1.0mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following the generalprocedure D.

LC-MS (m/z): 361 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 2.36 (s, 3H), 6.94-6.98 (m, 2H), 7.05(m, 4H), 7.19 (m, 1H), 7.31 (d, J=4.0 Hz, 1H), 7.37 (d, J=8.4 Hz, 1H),8.43 (d, J=8.4 Hz, 1H), 10.23 (br, 2H).

Example 27 N-[2-(3,4-Dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(3,4-Dimethoxyphenoxy)-1-nitrobenzene (0.93 g, 68%) was prepared from3,4-dimethoxyphenol (0.85 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71g, 5.0 mmol) following the general procedure A. This was reduced to2-(3,4-dimethoxyphenoxy)aniline (0.51 g, 62%) following generalprocedure B. N-[2-(3,4-Dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea(128 mg, 69%) was prepared from 2-(3,4-dimethoxyphenoxy)aniline (123 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 373 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.80 (s, 6H), 6.54 (dd, J=8.4, 2.4 Hz,1H), 6.78 (d, J=2.4 Hz, 1H), 6.82 (d., J=8.0 Hz, 1H), 6.97 (d, J=8.0 Hz,1H), 6.99-7.01 (m, 1H), 7.04 (d, J=3.6 Hz, 1H), 7.07-7.12 (m, 1H),7.33-7.34 (d, J=3.6 Hz, 1H), 8.39 (dd, J=8.0, 1.2 Hz, 1H), 8.90 (br,1H), 10.23 (br, 1H).

Example 28 N-[2-(3,4-Methylenedioxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(3,4-Methylenedioxyphenoxy)-1-nitrobenzene (0.75 g, 58%) was preparedfrom 3,4-methylenedioxyphenol (0.76 g, 5.5 mmol) and1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the generalprocedure A. This was reduced to 2-(3,4-methylenedioxyphenoxy)-aniline(0.47 g, 71%) following general procedure B.N-[2-(3,4-Methylenedioxyphenoxy)-phenyl]-N′-(thiazol-2-yl)urea (120 mg,68%) was prepared from 2-(3,4-methylenedioxy-phenoxy)aniline (115 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 357 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.06 (s, 2H), 6.51 (dd, J=8.4, 2.4 Hz,1H), 6.67 (d, J=2.4 Hz, 1H), 6.84-6.87 (m, 2H), 6.99-7.05 (m, 2H),7.10-7.14 (m, 1H), 7.32-7.33 (d, J=3.6 Hz, 1H), 8.39 (dd, J=8.0, 1.2 Hz,1H), 8.95 (br, 1H), 10.22 (br, 1H).

Example 29 N-[2-(2,4-Dichlorophenoxy)phenyl]-N′-(thiazol-2-yl)urea

N-[2-(2,4-Dichlorophenoxy)phenyl]-N′-(thiazol-2-yl)urea (125 mg, 67%)was prepared from 2-(2,4-dichlorophenoxy)aniline (127 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 382 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.86 (d, J=8.0 Hz, 1H) 7.03-7.08 (m,3H), 7.19-7.23 (m, 1H), 7.30 (d, J=4.0 Hz, 1H), 7.38 (dd, J=8.8, 2.8 Hz,1H), 7.65 (d, J=2.4 Hz, 1H), 8.43 (dd, J=8.0, 1.2 Hz, 1H), 8.87 (br,1H), 10.16 (br, 1H).

Example 30 N-[2-(2,4-Difluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2,4-Difluorophenoxy)-1-nitrobenzene (0.95 g, 76%) was prepared from2,4-di-fluorophenol (0.72 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71g, 5.0 mmol) following the general procedure A. This was reduced to2-(2,4-difluorophenoxy)aniline (0.53 g, 63%) following general procedureB. N-[2-(2,4-Difluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea (120 mg, 69%)was prepared from 2-(2,4-difluorophenoxy)aniline (110 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 349 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.83 (m, 1H), 7.00-7.30 (m, 6H), 7.32(d, J=3.6 Hz, 1H), 8.42 (dd, J=8.0, 2.0 Hz, 1H), 9.00 (br, 1H), 10.19(br, 1H).

Example 31 N-[2-(4-Fluoro-2-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(4-Fluoro-2-methoxyphenoxy)-1-nitrobenzene (0.88 g, 67%) was preparedfrom 4-fluoro-2-methoxyphenol (0.78 g, 5.5 mmol) and1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the generalprocedure A. This was reduced to 2-(4-fluoro-2-methoxyphenoxy)-aniline(0.60 g, 78%) following general procedure C.N-[2-(4-Fluoro-2-methoxyphenoxy)-phenyl]-N′-(thiazol-2-yl)urea (127 mg,71%) was prepared from 2-(4-fluoro-2-methoxy-phenoxy)aniline (116 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 361 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.82 (s, 3H), 6.61 (dd, J=8.0, 2.8 Hz,1H), 6.74-6.79 (m, 1H), 6.89-6.94 (m, 1H), 7.00-7.06 (m, 3H), 7.16 (dd,J=8.8, 5.6 Hz, 1H), 7.33 (d, J=3.6 Hz, 1H), 8.43 (dd, J=8.4, 1.6 Hz,1H), 8.85 (br, 1H), 10.29 (br, 1H).

Example 32N-[2-(4-Methoxy-2-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-[4-Methoxy-2-methoxycarbonylphenoxy]-1-nitrobenzene (0.78 g, 52%) wasprepared from methyl 5-methoxysalicylate (1.0 g, 5.5 mmol) and1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the generalprocedure A. This was reduced to2-[4-methoxy-2-(methoxycarbonyl)phenoxy]aniline (0.47 g, 68%) followinggeneral procedure B.N-[2-(4-Methoxy-2-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea(130 mg, 66%) was prepared from2-[4-methoxy-2-(methoxycarbonyl)phenoxy]aniline (136 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 401 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.69 (s, 3H), 3.84 (s, 3H), 6.61 (dd,J=8.0, 1.6 Hz, 1H), 6.90-6.95 (m, 1H), 7.03-7.09 (m, 2H), 7.16-7.25 (m,2H), 7.25-7.39 (m, 1H), 7.43-7.44 (m, 1H), 8.37 (dd, J=8.4, 1.6 Hz, 1H),8.96 (br, 1H), 10.26 (br, 1H).

Example 33 N-[2-(3-Methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(3-Methoxyphenoxy)-1-nitrobenzene (0.84 g, 69%) was prepared from3-methoxy-phenol (0.68 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71 g,5.0 mmol) following the general procedure A. This was reduced to2-(3-methoxyphenoxy)aniline (0.51 g, 70%) following general procedure B.N-[2-(3-Methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea (136 mg, 68%) wasprepared from 2-(3-methoxyphenoxy)aniline (108 mg, 0.5 mmol) and2-amino-thiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 343 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.78 (s, 3H), 6.55-6.62 (m, 2H),6.71-6.73 (m, 1H), 6.95 (dd, J=8.0, 1.6 Hz, 1H), 7.03-7.07 (m, 2H),7.16-7.20 (m, 1H), 7.27 (d, J=8.4 Hz, 1H), 7.31 (d, J=4.0 Hz, 1H), 8.43(dd, J=8.4, 1.6 Hz, 1H), 8.84 (br, 1H), 10.37 (br, 1H).

Example 34 N-[2-(3-Fluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(3-Fluorophenoxy)-1-nitrobenzene (0.85 g, 73%) was prepared from3-fluoro-phenol (0.62 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71 g,5.0 mmol) following the general procedure A. This was reduced to2-(3-fluorophenoxy)aniline (0.50 g, 68%) following general procedure B.N-[2-(3-Fluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea (110 mg, 68%) wasprepared from 2-(3-fluorophenoxy)aniline (102 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 331 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.80-6.84 (m, 2H), 6.85-6.93 (m, 1H),7.03-7.07 (m, 2H), 7.08-7.13 (m, 1H), 7.30 (d, J=3.6 Hz, 1H), 7.38-7.45(m, 1H), 8.45 (dd, J=8.0, 1.2 Hz, 1H), 9.06 (br, 1H), 10.1 (br 1H).

Example 35 N-[2-(3-Trifluoromethylphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-[3-(Trifluoromethyl)phenoxy]-1-nitrobenzene (0.92 g, 65%) was preparedfrom 3-hydroxybenzotrifluoride (0.89 g, 5.5 mmol) and1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the generalprocedure A. This was reduced to 2-[3-(trifluoromethyl)phenoxy]aniline(0.56 g, 68%) following general procedure B.N-[2-(3-Trifluoromethylphenoxy)phenyl]-N′-(thiazol-2-yl)urea (120 mg,62%) was prepared from 2-[3-(trifluoromethyl)phenoxy]aniline (127 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 381 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 7.04-7.13 (m, 3H), 7.24-7.29 (m, 3H),7.36 (s, 1H), 7.47 (d, J=7.6 Hz, 1H), 7.63 (t, J=8.0 Hz, 1H), 8.46 (dd,J=8.0, 1.2 Hz, 1H), 8.95 (br, 1H), 10.08 (br, 1H).

Example 36 N-[2-(2-Methylphenoxy)phenyl]-N′-(thiazol-2-yl)urea

N-[2-(2-Methylphenoxy)phenyl]-N′-(thiazol-2-yl)urea (110 mg, 68%) wasprepared from 2-(2-methylphenoxy)aniline (100 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 327 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 2.25 (s, 3H), 6.68 (d, J=8.4 Hz, 1H),6.89 (d, J=8.0 Hz, 1H), 6.96-7.00 (m, 1H), 7.04-7.13 (m, 3H), 7.20-7.34(m, 3H), 8.42 (dd, J=8.0, 1.6 Hz, 1H), 8.95 (br, 1H), 10.25 (br, 1H).

Example 37 N-[2-(2-Methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2-Methoxyphenoxy)-1-nitrobenzene (0.99 g, 81%) was prepared from2-methoxy-phenol (0.68 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71 g,5.0 mmol) following the general procedure A. This was reduced to2-(2-methoxyphenoxy)aniline (0.63 g, 73%) following general procedure B.N-2-(2-Methoxyphenoxy)phenyl-N′-(thiazol-2-yl)urea (110 g, 65%) wasprepared from 2-(2-methoxyphenoxy)aniline (108 mg, 0.5 mmol) and2-amino-thiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 343 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.78 (s, 3H), 6.61 (d, J=8.0 Hz, 1H),6.91-7.33 (m, 8H), 8.37 (d, J=8.0 Hz, 1H), 9.13 (br, 1H), 10.31 (br,1H).

Example 38 N-[2-(2-Isopropoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2-Isopropoxyphenoxy)-1-nitrobenzene (0.90 g, 69%) was prepared from2-iso-propoxyphenol (0.84 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71g, 5.0 mmol) following the general procedure A. This was reduced to2-(2-methoxyphenoxy)aniline (0.65 g, 81%) following general procedure B.N-[2-(2-Isopropoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea (120 mg, 65%)was prepared from 2-(2-isopropoxyphenoxy)aniline (122 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 371 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 1.07 (d, J=6.0 Hz, 6H), 4.54-4.59 (m,1H), 6.64 (dd, J=8.0, 1.6 Hz, 1H), 6.88-6.92 (m, 1H), 6.97-7.06 (m, 3H),7.12-7.22 (m, 3H), 7.33 (d, J=3.6 Hz, 1H), 8.38 (dd, J=8.0, 1.6 Hz, 1H),8.86 (br, 1H), 10.3 (br, 1H).

Example 39 N-[2-(2-Fluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2-Fluorophenoxy)-1-nitrobenzene (0.94 g, 81%) was prepared from2-fluorophenol (0.62 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71 g,5.0 mmol) following the general procedure A. This was reduced to2-(2-fluorophenoxy)aniline (0.59 g, 72%) following general procedure B.N-[2-(2-Fluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea (110 mg, 68%) wasprepared from 2-(2-fluorophenoxy)aniline (102 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS: 331 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.84 (d, J=8.0 Hz, 1H) 7.05-7.08 (m,1H), 7.01-7.06 (m, 2H), 7.12-7.17 (m, 2H), 7.22-7.25 (m, 2H), 7.29-7.36(m, 2H), 8.43 (dd, J=8.0, 1.6 Hz, 1H), 8.95 (br, 1H), 10.17 (br, 1H).

Example 40 N-[2-(2-Methylsulfanylphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2-Methylsulfanylphenoxy)-1-nitrobenzene (0.88 g, 68%) was preparedfrom 2-hydroxythioanisole (0.77 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene(0.71 g, 5.0 mmol) following the general procedure A. This was reducedto 2-(2-methylsulfanylphenoxy)aniline (0.53 g, 68%) following generalprocedure B. N-[2-(2-Methylsulfanylphenoxy)phenyl]-N′-(thiazol-2-yl)urea(115 mg, 65%) was prepared from 2-(2-methylsulfanylphenoxy)aniline (115mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 359 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 2.42 (s, 3H), 6.68 (dd, J=8.0, 1.2 Hz,1H), 6.92 (d, J=8.0 Hz, 1H), 6.95-6.99 (m, 1H), 7.04 (d, J=3.6 Hz, 1H),7.09-7.14 (m, 1H), 7.17-7.26 (m, 2H), 7.31 (d, J=3.6 Hz, 1H), 7.38 (dd,J=7.6, 1.6 Hz, 1H), 8.42 (dd, J=8.0, 1.6 Hz, 1H), 8.95 (br, 1H), 10.26(br, 1H).

Example 41 N-[2-(2-Methylsulfonylphenoxy)phenyl]-N′-thiazolylurea

To a solution of 2-(2-methylsulfanylphenoxy)-1-nitrobenzene (1.3 g, 5.0mmol) in di-chloromethane (30 ml) at 0° C. was added mCPBA (70%, 3.68 g,15 mmol), in portions during 10 min. The contents were stirred for 2 hat room temperature. The precipitate was filtered off and the motherliquor was washed thrice with 10% aq Na₂S₂O₇. The organic layer waswashed (dil NaOH, water, brine), dried and concentrated to obtain2-(2-methylsulfonyl-phenoxy)-1-nitrobenzene (1.0 g, 68%). This wasreduced to 2-(2-methylsulfonylphenoxy)-aniline (0.68 g, 76%) followinggeneral procedure B.N-[2-(2-Methylsulfonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea (105 mg,55%) was prepared from 2-(2-methylsulfonylphenoxy)aniline (132 mg, 0.5mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 391 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.44 (s, 3H), 7.02 (d, J=3.6 Hz, 1H),7.06 (d, J=8.4 Hz, 1H), 7.12-7.20 (m, 2H), 7.27-7.36 (m, 2H), 7.38-7.40(m, 1H), 7.67-7.71 (m, 1H), 8.02 (dd, J=8.0, 1.6 Hz, 1H), 8.42 (dd,J=8.4, 1.2 Hz, 1H), 9.20 (br, 1H), 9.78 (br, 1H).

Example 42 N-[2-(2-Trifluoromethylphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-[2-(Trifluoromethyl)phenoxy]-1-nitrobenzene (0.92 g, 65%) was preparedfrom 2-hydroxybenzotrifluoride (0.89 g, 5.5 mmol) and1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the generalprocedure A. This was reduced to 2-[2-(trifluoromethyl)phenoxy]aniline(0.56 g, 68%) following general procedure B.N-[2-(2-Trifluoromethylphenoxy)phenyl]-N′-(thiazol-2-yl)urea (115 mg,61%) was prepared from 2-[2-(trifluoromethyl)phenoxy]aniline (127 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 381 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.91 (dd, J=8.0, 1.6 Hz, 1H), 7.01-7.06(m, 2H), 7.08-7.11 (m, 1H), 7.22-7.26 (m, 2H), 7.34 (t, J=7.6 Hz, 1H),7.65 (t, J=7.6 Hz, 1H), 7.81 (dd, J=8.0, 1.2 Hz, 1H), 8.45 (dd, J=8.4,1.6 Hz, 1H), 9.00 (br, 1H), 10.2 (br, 1H).

Example 43 N-[2-(2,6-Dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2,6-Dimethoxyphenoxy)-1-nitrobenzene (0.85 g, 63%) was prepared from2,6-di-methoxyphenol (0.85 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene(0.71 g, 5.0 mmol) following the general procedure A. This was reducedto 2-(2,6-dimethoxyphenoxy)aniline (0.51 g, 68%) following generalprocedure C. N-[2-(2,6-Dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)-urea(117 g, 63%) was prepared from 2-(2,6-dimethoxyphenoxy)aniline (123 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 373 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.76 (s, 3H), 6.49 (dd, J=8.4, 1.2 Hz,1H), 6.80 (d, J=8.4 Hz, 2H), 6.84-6.88 (m, 1H), 6.95-6.99 (m, 1H), 7.04(d, J=3.2 Hz, 1H), 7.22 (t, J=8.4 Hz, 1H), 7.35 (d, J=3.6 Hz, 1H), 8.33(dd, J=8.0, 1.6 Hz, 1H), 8.85 (br, 1H), 10.40 (br, 1H).

Example 44 N-[2-(2,6-difluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2,6-difluorophenoxy)-1-nitrobenzene (0.44 g, 70%) was prepared from2,6-difluorophenol (0.32 g, 2.5 mmol) and 1-fluoro-2-nitrobenzene (0.36g, 2.5 mmol) following the general procedure A. This was reduced to2-(2,6-difluorophenoxy)aniline (0.24 g, 60%) following general procedureB. N-[2-(2,6-difluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea (133 mg, 60%)was prepared from 2-(2,6-difluorophenoxy)aniline (206 mg, 0.9 mmol) and2-aminothiazole (405 mg, 2.5 mmol) following the general procedure D.

LC-MS (m/z): 349 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.73 (d, J=8 Hz, 1H), 6.98 (m, 1H), 7.06(d, J=3.2 Hz, 1H), 7.12 (m, 1H), 7.20-7.28 (m, 2H), 7.25 (d, J=3.6 Hz,1H), 7.40 (m, 1H), 8.43 (d, J=8.2 Hz, 1H), 9.05 (br, 1H), 10.12 (br,1H).

Example 45 N-[2-(2-Fluoro-6-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2-Fluoro-6-methoxyphenoxy)-1-nitrobenzene (0.84 g, 64%) was preparedfrom 2-fluoro-6-methoxyphenol (0.78 g, 5.5 mmol) and1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the generalprocedure A. This was reduced to 2-(2-fluoro-6-methoxyphenoxy)-aniline(0.63 g, 85%) following general procedure C.N-2-(2-Fluoro-6-methoxyphenoxy)-phenyl)-N′-(thiazol-2-yl)urea (114 mg,63%) was prepared from 2-(2-fluoro-6-methoxy-phenoxy)aniline (117 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 361 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.82 (s, 3H), 6.59 (m, 1H), 6.89-6.96(m, 2H), 7.02-7.07 (m, 3H), 7.27-7.33 (m, 1H), 7.34 (d, J=3.6 Hz, 1H),8.38 (dd, J=8.4, 1.6 Hz, 1H), 8.85 (br, 1H), 10.31 (br, 1H).

Example 46N-[2-(2-Methoxy-6-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2-Methoxy-6-methoxycarbonylphenoxy)-1-nitrobenzene (1.24 g, 82%) wasprepared from methyl 3-methoxysalicylate (1.0 g, 5.5 mmol) and1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the generalprocedure A. This compound was reduced to2-(2-methoxy-6-methoxycarbonylphenoxy)aniline (0.89 g, 80%) followingthe general procedure C.N-[2-(2-Methoxy-6-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea(143 mg, 72%) was prepared from2-(2-methoxy-6-methoxycarbonylphenoxy)aniline (136 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 401 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.78 (s, 3H), 3.87 (s, 3H), 6.89-6.97(m, 1H), 7.04-7.23 (m, 3H), 7.36-7.47 (m, 2H), 7.67-7.76 (m, 2H), 8.17(dd, J=1.6, 10.8 Hz, 1H), 8.78 (br, 1H), 10.64 (br, 1H).

Example 47N-[(3-methoxy-2-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(3-Methoxy-2-methoxycarbonylphenoxy)-1-nitrobenzene (1.21 g, 80%) wasprepared from methyl 6-methoxysalicylate (1.09 g, 5.5 mmol) and1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the generalprocedure A. This compound was reduced to2-(3-methoxy-2-methoxycarbonylphenoxy)aniline (0.82 g, 75%) followingthe general procedure C.N-[(3-methoxy-2-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea(130 mg, 65%) was prepared from2-(3-methoxy-2-methoxycarbonylphenoxy)aniline (136 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 401 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.66 (s, 3H), 3.80 (s, 3H), 6.44-6.46(m, 1H), 6.83-6.87 (m, 1H), 6.96-6.99 (m, 1H), 7.03 (d, J=3.6 Hz, 1H),7.33 (d, J=4 Hz, 1H), 7.37-7.46 (m, 2H), 7.46-7.48 (m, 1H), 8.32-8.35(dd, J=1.6, 8.0 Hz, 1H), 8.80 (br, 1H), 10.32 (br, 1H).

Example 48 N-[2-(2,3-Dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2,3-Dimethoxyphenoxy)-1-nitrobenzene (0.88 g, 64%) was prepared from2,3-dimethoxyphenol (0.85 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71g, 5.0 mmol) following the general procedure A. This was reduced to2-(2,3-dimethoxyphenoxy)aniline (0.57 g, 73%) following generalprocedure B. N-[2-(2,3-Dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea(131 g, 71%) was prepared from 2-(2,3-dimethoxyphenoxy)aniline (123 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 373 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.66 (s, 3H), 3.88 (s, 3H), 6.66-6.74(m, 2H), 6.91-6.98 (m, 2H), 7.04-7.16 (m, 3H), 7.32 (d, J=3.6 Hz, 1H),8.39 (dd, J=8.0, 1.6 Hz, 1H), 8.90 (br, 1H), 10.26 (br, 1H).

Example 49 N-[2-(2,3,4-Trichlorophenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2,3,4-Trichlorophenoxy)-1-nitrobenzene (1.04 g, 65%) was preparedfrom 2,3,4-trichlorophenol (0.98 g, 5.0 mmol) and1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the generalprocedure A. This was reduced to 2-(2,3,4-trichlorophenoxy)aniline (0.42g, 60%, 2.5 mmol scale) following general procedure B.N-[2-(2,3,4-Trichlorophenoxy)phenyl]-N′-(thiazol-2-yl)urea (343 mg, 55%)was prepared from 2-(2,3,4-trichlorophenoxy)aniline (420 mg, 1.5 mmol)and 2-aminothiazole (150 mg, 1.5 mmol) following the general procedureD.

LC-MS (m/z): 415 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 9.97-7.12 (m, 4H), 7.23-7.28 (m, 2H),7.58 (d, J=8.8 Hz, 1H), 8.45 (d, J=8.0 Hz, 1H), 10.13 (br, 1H).

Example 50 N-[2-(2,4,6-Trifluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2,4,6-Trifluorophenoxy)-1-nitrobenzene (1.14 g, 85%) was preparedfrom 2,4,6-trifluorophenol (0.74 g, 5.0 mmol) and1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the generalprocedure A. This was reduced to 2-(2,4,6-trifluorophenoxy)aniline (0.42g, 70%, 2.5 mmol scale) following general procedure B.N-[2-(2,4,6-Trifluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea (219 mg, 60%)was prepared from 2-(2,4,6-trifluorophenoxy)aniline (237 mg, 1.0 mmol)and 2-aminothiazole (100 mg, 1.0 mmol) following the general procedureD.

LC-MS (m/z): 367 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.78 (d, J=8.4 Hz, 1H), 7.00-7.21 (m,5H), 7.36 (d, J=3.6 Hz, 1H), 8.42 (d, J=8.4 Hz, 1H), 9.05 (br, 1H),10.36 (br, 1H).

Example 51 N-[2-(2,4-dichloronaphth-1-oxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2,4-Dichloronaphth-1-oxy)-1-nitrobenzene (1.17 g, 60%) was preparedfrom 2,4-dichloronaphth-1-ol (1.06 g, 5.0 mmol) and1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the generalprocedure A. This was reduced to 2-(2,4-dichloronaphth-1-oxy)aniline(0.45 g, 60%, 2.5 mmol scale) following general procedure B.N-[2-(2,4-Dichloronaphth-1-oxy)phenyl]-N′-thiazolylurea (172 g, 40%) wasprepared from 2-(2,4-dichloronaphth-1-oxy)aniline (303 mg, 1.0 mmol) and2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

LC-MS (m/z): 431 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.39 (d, J=8.2 Hz, 1H), 6.86 (m, 1H),7.07 (m, 2H), 7.34 (d, J=3.6 Hz, 1H), 7.71-7.88 (m, 3H), 8.00 (d, J=8.0Hz, 1H), 8.32 (d, J=8.0 Hz, 1H), 8.48 (d, J=8.0 Hz, 1H), 9.15 (br, 1H),10.35 (br, 1H).

Example 52N-[2-(2-Methoxyphenoxy)-5-(methylsulfonyl)phenyl]-N′-(thiazol-2-yl)urea

2-(2-Methoxyphenoxy)-5-(methylsulfonyl)-1-nitrobenzene (1.21 g, 75%) wasprepared from 2-methoxyphenol (0.68 g, 5.5 mmol) and1-fluoro-4-methylsulfonyl-2-nitro-benzene (1.09 g, 5.0 mmol) followingthe general procedure A. This was reduced to2-(2-methoxyphenoxy)-5-(methylsulfonyl)aniline (0.68 g, 62%) followinggeneral procedure B.N-[2-(2-Methoxyphenoxy)-5-(methylsulfonyl)phenyl]-N′-(thiazol-2-yl)urea(136 mg, 65%) was prepared from2-(2-methoxyphenoxy)-5-(methylsulfonyl)aniline (146 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 421 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 2.82 (s, 3H), 3.77 (s, 3H), 6.73 (d,J=8.4 Hz, 1H) 7.05-7.11 (m, 2H), 7.23-7.28 (m, 2H), 7.32-7.37 (m, 2H),7.50 (dd, J=8.4, 3.6 Hz, 1H), 9.02 (d, J=2.4 Hz, 1H), 9.12 (br, 1H),10.42 (br, 1H).

Example 53 N-[5-Cyano-2-(2-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

4-(2-Methoxyphenoxy)-3-nitrobenzonitrile (1.10 g, 81%) was prepared from2-methoxyphenol (0.68 g, 5.5 mmol) and 4-fluoro-3-nitrobenzonitrile(1.33 g, 5.0 mmol) following general procedure A. This was reduced to4-(2-methoxyphenoxy)-3-aminobenzo-nitrile (0.62 g, 63%) followinggeneral procedure B.N-[5-Cyano-2-(2-methoxyphenoxy)-phenyl]-N′-(thiazol-2-yl)urea (130 mg,71%) was prepared from 4-(2-methoxyphenoxy)-3-aminobenzonitrile (120 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following generalprocedure D.

LC-MS (m/z): 368 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.79 (s, 3H), 6.69 (d, J=8.4 Hz, 1H)7.05-7.09 (m, 1H), 7.10 (d, J=3.6 Hz, 1H), 7.22-7.27 (m, 2H), 7.32-7.36(m, 3H), 8.75 (d, J=2.0 Hz, 1H), 9.12 (br, 1H), 10.38 (br, 1H).

Example 54N-[5-Fluoro-2-(2-methylsulfanylphenoxy)phenyl]-N′-thiazolylurea

5-Fluoro-2-(2-methylsulfanylphenoxy)-1-nitrobenzene (0.95 g, 68%) wasprepared from 2-hydroxythioanisole (0.77 g, 5.5 mmol) and2,5-difluoro-1-nitrobenzene (0.80 g, 5.0 mmol) following the generalprocedure A. This was reduced to5-fluoro-2-(2-methylsulfanyl-phenoxy)aniline (0.52 g, 62%) followinggeneral procedure B.N-[5-Fluoro-2-(2-methyl-sulfanylphenoxy)phenyl]-N′-(thiazol-2-yl)urea(120 mg, 65%) was prepared from5-fluoro-2-(2-methylsulfanylphenoxy)aniline (125 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 377 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 2.48 (s, 3H), 6.61 (m, 2H), 6.92 (d,J=7.6 Hz, 1H), 7.06 (d, J=3.6 Hz, 1H), 7.16-7.25 (m, 2H), 7.31 (d, J=3.6Hz, 1H), 7.39 (dd, J=7.6, 2.0 Hz, 1H), 8.26-8.29 (m, 1H), 9.00 (br, 1H),10.32 (br, 1H).

Example 55N-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)-1-nitrobenzene (0.91 g, 65%) wasprepared from 2-fluoro-6-methoxyphenol (0.78 g, 5.5 mmol) and2,5-difluoro-1-nitrobenzene (0.80 g, 5.0 mmol) following the generalprocedure A. This was reduced to5-fluoro-2-(2-fluoro-6-methoxyphenoxy)aniline (0.66 g, 81%) followinggeneral procedure C.N-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea(130 g, 69%) was prepared from5-fluoro-2-(2-fluoro-6-methoxyphenoxy)aniline (126 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 379 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.83 (s, 3H), 6.60-6.70 (m, 2H),6.92-6.97 (m, 1H), 7.03-7.05 (m, 1H), 7.09 (d, J=4.0 Hz, 1H), 7.27-7.33(m, 1H), 7.36 (d, J=3.6 Hz, 1H), 8.23 (dd, J=10.8, 3.2 Hz, 1H), 9.05(br, 1H), 10.39 (br, 1H).

Example 56N-[2-(2,3-Dimethoxyphenoxy)-5-fluorophenyl]-N′(thiazol-2-yl)urea

2-(2,3-Dimethoxyphenoxy)-5-fluoro-1-nitrobenzene (1.0 g, 68%) wasprepared from 2,3-dimethoxyphenol (0.85 g, 5.5 mmol) and2,5-difluoro-1-nitrobenzene (0.80 g, 5.0 mmol) following the generalprocedure A. This was reduced to2-(2,3-dimethoxyphenoxy)-5-fluoro-aniline (0.67 g, 75%) followinggeneral procedure C.N-[2-(2,3-Dimethoxyphenoxy)-5-fluoro-phenyl]-N′-(thiazol-2-yl)urea (126g, 65%) was prepared from 2-(2,3-dimethoxyphenoxy)-5-fluoroaniline (132mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 391 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.68 (s, 3H), 3.88 (s, 3H), 6.67 (dd,J=9.2, 1.2 Hz, 1H), 6.70-6.79 (m, 2H), 6.92 (dd, J=8.0, 1.6 Hz, 1H),7.05-7.09 (m, 2H), 7.32 (d, J=3.6 Hz, 1H), 8.25 (dd, J=11.2, 2.8 Hz,1H), 9.03 (br, 1H), 10.33 (br, 1H).

Example 57N-[2-(3,4-Difluorophenoxy)-5-fluorophenyl]-N′-(thiazol-2-yl)urea

2-(3,4-Difluorophenoxy)-5-fluoro-1-nitrobenzene (1.05 g, 78%) wasprepared from 3,4-difluorophenol (0.72 g, 5.5 mmol) and2,5-difluoro-1-nitrobenzene (0.8 g, 5.0 mmol) following the generalprocedure A. This compound was reduced to2-(3,4-difluorophenoxy)-5-fluoroaniline (0.63 g, 68%) following thegeneral procedure B.N-[2-(3,4-Difluorophenoxy)-5-fluorophenyl]-N′-(thiazol-2-yl)urea (132mg, 72%) was prepared from 2-(3,4-difluoro-phenoxy)-5-fluoroaniline (120mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 367 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.81-6.89 (m, 2H), 7.05-7.11 (m, 3H),7.31-7.38 (m, 2H), 8.28 (dd, J=2.8, 10.8 Hz, 1H), 9.10 (br, 1H), 10.34(br, 1H).

Example 58 N-[5-Fluoro-2-(4-fluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea

5-Fluoro-2-(4-fluorophenoxy)-1-nitrobenzene (0.94 g, 75%) was preparedfrom 4-fluorophenol (0.62 g, 5.5 mmol) and 2,5-difluoro-1-nitrobenzene(0.71 g, 5.0 mmol) following the general procedure A. This compound wasreduced to 2-(4-fluorophenoxy)-5-fluoroaniline (0.53 g, 64%) followingthe general procedure B.N-[5-Fluoro-2-(4-fluorophenoxy)phenyl]-N′-(thiazol-2-yl)urea (130 mg,75%) was prepared from 5-fluoro-2-(4-fluorophenoxy)aniline (110 mg, 0.5mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 349 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.78-6.82 (m, 1H), 6.93-6.97 (m, 1H),7.06-7.10 (m, 3H), 7.14-7.18 (m, 2H), 7.3 (d, J=3.2 Hz, 1H), 8.27 (dd,J=2.8, 10.8 Hz, 1H), 8.82 (br, 1H), 10.28 (br, 1H).

Example 59N-[2-(2,4-Dichlorophenoxy)-5-fluorophenyl]-N′-(thiazol-2-yl)urea

2-(2,4-Dichlorophenoxy)-5-fluoro-1-nitrobenzene (1.17 g, 78%) wasprepared from 2,4-dichlorophenol (0.89 g, 5.5 mmol) and2,5-difluoro-1-nitrobenzene (0.8 g, 5.0 mmol) following the generalprocedure A. This compound was reduced to2-(2,4-dichlorophenoxy)-5-fluoroaniline (0.68 g, 64%) following thegeneral procedure B.N-[2-(2,4-Dichlorophenoxy)-5-fluorophenyl]-N′-(thiazol-2-yl)urea (150mg, 76%) was prepared from 2-(2,4-dichloro-phenoxy)-5-fluoroaniline (135mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 399 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.79-6.84 (m, 1H), 6.93 (m, 1H),7.03-7.07 (m, 2H), 7.30 (d, J=3.2 Hz, 1H), 7.38 (dd, 2.4, 8.8 Hz 1H),7.64 (d, J=2.4 Hz, 1H), 8.29 (dd, J=2.4, 11.2 Hz 1H), 9.00 (br, 1H),10.24 (bs, 1H).

Example 60 N-[5-Fluoro-2-(4-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

5-Fluoro-2-(4-methoxyphenoxy)-1-nitrobenzene (1.05 g, 80%) was preparedfrom 4-methoxyphenol (0.68 g, 5.5 mmol) and 2,5-difluoro-1-nitrobenzene(0.8 g, 5.0 mmol) following the general procedure A. This compound wasreduced to 5-fluoro-2-(4-methoxy-phenoxy)aniline (0.62 g, 66%) followingthe general procedure B.N-[5-Fluoro-2-(4-methoxy-phenoxy)phenyl]-N′-(thiazol-2-yl)urea (133 mg,74%) was prepared from 2-(4-methoxy-phenoxy)-5-fluoroaniline (117 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 361 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.79 (s, 3H), 6.75-6.77 (m, 1H),6.82-6.87 (m, 1H), 6.94-7.01 (m, 3H), 7.07 (d, J=2.1 Hz, 1H), 7.32 (d,J=3.6 Hz, 1H), 8.26 (dd, J=3.2, 11.2 Hz, 1H), 9.05 (br, 1H), 10.32 (br,1H).

Example 61 N-[5-Fluoro-2-(2-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

5-Fluoro-2-(2-methoxyphenoxy)-1-nitrobenzene (1.07 g, 81%) was preparedfrom 2-methoxyphenol (0.62 g, 5.5 mmol) and 2,5-difluoro-1-nitrobenzene(0.8 g, 5.0 mmol) following the general procedure A. This compound wasreduced to 2-(2-methoxyphenoxy)-5-fluoroaniline (0.58 g, 66%) followingthe general procedure B.1-[5-Fluoro-2-(2-methoxy-phenoxy)phenyl]-3-(thiazol-2-yl)urea (129 mg,72%) was prepared from 5-fluoro-2-(2-methoxyphenoxy)aniline (117 mg, 0.5mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 361 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.79 (s, 3H), 6.65-6.7 (m, 2H),6.98-7.01 (m, 1H), 7.05-7.22 (m, 4H), 7.32 (d, J=3.6 Hz, 1H), 8.22 (dd,J=2.8, 10.8 Hz, 1H), 9.12 (br, 1H), 10.42 (br, 1H).

Example 62N-[5-Fluoro-2-(2-trifluoromethylphenoxy)phenyl]-N′-(thiazol-2-yl)urea

5-Fluoro-2-(2-trifluoromethylphenoxy)-1-nitrobenzene (1.17 g, 78%) wasprepared from 2-hydroxybenzotrifluoride (0.89 g, 5.5 mmol) and2,5-difluoro-1-nitrobenzene (0.8 g, 5.0 mmol) following the generalprocedure A. This compound was reduced to5-fluoro-2-(2-tri-fluoromethylphenoxy)-aniline (0.65 g, 62%) followingthe general procedure B.N-[5-Fluoro-2-(2-trifluoromethylphenoxy)phenyl]-N′-(thiazol-2-yl)urea(146 mg, 74%) was prepared from2-(2-trifluoromethylphenoxy)-5-fluoroaniline (135 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 399 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.81-6.87 (m, 1H), 6.95-7.05 (m, 3H),7.21 (m, 1H), 7.31-7.36 (m, 1H), 7.6-7.65 (m, 1H), 7.79 (d, J=7.6 Hz,1H), 8.30 (dd, J=3.2, 11.2 Hz, 1H), 8.72 (br, 1H), 10.24 (br, 1H).

Example 63 N-[5-Fluoro-2-(naphth-2-oxy)phenyl]-N′-(thiazol-2-yl)urea

5-Fluoro-2-(naphth-2-oxy)-1-nitrobenzene (1.13 g, 80%) was prepared from2-naphthol (0.79 g, 5.5 mmol) and 2,5-difluoro-1-nitrobenzene (0.8 g,5.0 mmol) following the general procedure A. This compound was reducedto 2-(2-naphth-2-oxy)-5-fluoroaniline (0.64 g, 64%) following thegeneral procedure B.N-[5-Fluoro-2-(naphth-2-oxy)phenyl]-N′-(thiazol-2-yl)urea (123 mg, 65%)was prepared from 5-Fluoro-2-(naphth-2-oxy)-aniline (127 mg, 0.5 mmol)and 2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 381 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.83-6.87 (m, 1H), 7.01 (bs, 1H), 7.08(m, 1H), 7.33 (bs, 1H), 7.42-7.49 (m, 3H), 7.80 (d, J=7.6 Hz, 1H), 7.90(d, J=7.6 Hz, 1H), 7.97 (d, J=8.8 Hz, 1H), 8.32 (d, J=8.4 Hz, 1H), 8.62(br, 1H), 10.22 (br, 1H)

Example 64N-[2-(2,3-Dimethoxyphenoxy)-6-fluorophenyl]-N′-(thiazol-2-yl)urea

2-(2,3-Dimethoxyphenoxy)-6-fluoro-nitrobenzene (1.05 g, 72%) wasprepared from 2,3-dimethoxyphenol (0.85 g, 5.5 mmol) and2,6-difluoronitrobenzene (0.80 g, 5.0 mmol) following the generalprocedure A. This compound was reduced to2-(2,3-dimethoxy-phenoxy)-6-fluoroaniline (0.66 g, 70%) following thegeneral procedure CN-[2-(2,3-Di-methoxyphenoxy)-6-fluorophenyl]-N′-(thiazol-2-yl)urea (136mg, 70%) was prepared from 2-(2,3-dimethoxyphenoxy)-6-fluoroaniline (131mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 391 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.64 (s, 3H), 3.85 (s, 3H), 6.59 (d,J=8.0 Hz, 1H), 6.68-6.69 (d, J=8.0 Hz, 1H), 6.88-7.06 (m, 4H), 7.22-7.22(m 1H), 7.30-7.31 (d, J=3.2 Hz, 1H), 8.18 (br, 1H), 10.26 (br, 1H).

Example 65 N-[2-(4-Fluoro-2-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

4-Fluoro-2-(2-methoxyphenoxy)-1-nitrobenzene (1.2 g, 91.6%) was preparedfrom 2-methoxyphenol (0.68 g, 5.5 mmol) and 2,4-difluoro-1-nitrobenzene(0.80 g, 5.0 mmol) following the general procedure F. The product wasthen reduced to 4-fluoro-2-(2-methoxy-phenoxy)aniline (0.96 g, 73%)following general procedure B.N-[4-Fluoro-2-(2-methoxy-phenoxy)phenyl]-N′-(thiazol-2-yl)urea (0.32 g,86%) was prepared from 4-fluoro-2-(2-methoxyphenoxy)aniline (0.117 g,0.5 mmol) and 2-aminothiazole (0.060 g, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 361 (M+1)⁺.

¹H NMR (400 MHz, CDCl₃): δ 3.78 (s, 3H), 6.32 (dd, J=4.0, 14.0 Hz, 1H),6.35 (dd, J=2.8, 10.4 Hz, 1H), 6.61 (t, J=4.0 Hz, 1H), 6.80 (m, 2H),7.05 (m, 2H), 7.18 (m, 2H), 11.46 (br, 2H).

Example 66N-[2-(2,3-Dimethoxyphenoxy)-4-fluorophenyl]-N′-(thiazol-2-yl)urea

2-(2,3-Dimethoxyphenoxy)-4-fluoro-1-nitrobenzene (0.88 g, 60%) wasprepared from 2,3-dimethoxyphenol (0.85 g, 5.5 mmol) and2,4-difluoro-1-nitrobenzene (0.8 g, 5.0 mmol) following the generalprocedure F. This compound was reduced to2-(2,3-dimethoxy-phenoxy)-4-fluoroaniline (0.52 g, 66%) following thegeneral procedure C.N-[2-(2,3-di-methoxyphenoxy)-4-fluorophenyl]-N′-(thiazol-2-yl)urea (116mg, 60%) was prepared from 2-(2,3-dimethoxyphenoxy)-4-fluoroaniline (132mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 391 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.68 (s, 3H), 3.89 (s, 3H), 6.46 (dd,J=2.4, 9.2 Hz, 1H), δ 6.76 (dd, J=1.6, 8.0 Hz, 1H), 6.82-6.87 (m, 1H),6.98 (dd, J=2.3, 6.8 Hz, 1H), 7.04 (d, J=3.6 Hz, 1H), 7.1-7.13 (t, J=8.4Hz, 1H), 7.31 (d, J=4.0 Hz, 1H), 8.33-8.37 (dd, J=6.4, 9.6 Hz, 1H), 8.42(br, 1H), 10.23 (br, 1H).

Example 67N-[4-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

4-Fluoro-2-(2-fluoro-6-methoxyphenoxy)-1-nitrobenzene (0.91 g, 65%) wasprepared from 2-fluoro-6-methoxyphenol (0.78 g, 5.5 mmol) and2,4-difluoro-1-nitrobenzene (0.8 g, 5.0 mmol) following the generalprocedure F. This compound was reduced to4-fluoro-2-(2-fluoro-6-methoxyphenoxy)aniline (0.61 g, 75%) followingthe general procedure C.N-[4-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea(122 mg, 65%) was prepared from4-fluoro-2-(2-fluoro-6-methoxyphenoxy)aniline (126 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 379 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.84 (s, 3H), 6.39 (dd, 2.8, 9.6 Hz 1H),6.81-6.85 (m, 1H), 6.95-6.98 (m, 1H), 7.05-7.07 (m, 2H) 7.29-7.35 (m,2H), 8.32-8.36 (m, 1H), 8.85 (br, 1H), 10.26 (br, 1H)

Example 68N-[2-(2-Fluoro-6-methoxyphenoxy)-4-methoxyphenyl]-N′-(thiazol-2-yl)urea

A mixture of 4-fluoro-2-(2-fluoro-6-methoxyphenoxy)-1-nitrobenzene (1.33g, 5 mmol) and sodium methoxide (035 g, 6 mmol) in DMF (10 ml) washeated at 80° C. for 2 h. The mixture was poured into water and wasextracted with ethyl acetate (3×20 ml). The combined organic layer waswashed with water, brine and dried (Na₂SO₄). The solution wasconcentrated under reduced pressure to obtain2-(2-fluoro-6-methoxyphenoxy)-4-methoxy-1-nitrobenzene (1.02 g, 70%).This compound was reduced to2-(2-fluoro-6-methoxyphenoxy)-4-methoxyaniline (0.62 g, 73%) followingthe general procedure C.N-[2-(2-Fluoro-6-methoxyphenoxy)-4-methoxyphenyl]-N′-(thiazol-2-yl)urea(136 mg, 70%) was prepared from2-(2-methoxy-6-fluorophenoxy)-4-methoxyaniline (132 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 391 (M+1)⁺.

¹H NMR (400 MHz, CDCl₃): δ 3.74 (s, 3H), 6.19 (bs, 1H), 6.46 (dd, J=2.4,7.6 Hz, 1H), 6.61-6.84 (m, 3H), 7.04-7.19 (m, 1H), 7.32-7.44 (bs, 1H),8.04-8.12 (m, 1H), 8.20 (br, 1H), 10.22 (br, 1H).

Example 69N-[3-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

Methyl 3-fluoro-2-(2-fluoro-6-methoxyphenoxy)benzoate (0.88 g, 60%) wasprepared from methyl 2,3-difluorobenzoate (0.86 g, 5 mmol) and2-fluoro-6-methoxyphenol (0.78 g, 5.5 mmol) as described in procedure A.Hydrolysis of this ester with LiOH in aqueous methanol furnished2-(2-methoxy-6-fluorophenoxy)-3-fluorobenzoic acid (0.86 g, 90%). To asolution of 3-fluoro-2-(2-fluoro-6-methoxyphenoxy)benzoic acid (0.56 g,2.0 mmol) in 1,2-dichloroethane (10 ml) was added oxalyl chloride (0.18ml, 2.2 mmol). The solution was stirred at room temperature for 45 min.To this solution was added NaN₃ (390 mg, 6 mmol) and the mixture washeated to reflux for 3 h. 2-Aminothiazole (200 mg, 2 mmol) was thenadded to this mixture and was further refluxed for 3 h. The mixture wasconcentrated and the residue was purified by column chromatography(silica, CH₂Cl₂ then 10% ethyl acetate in CH₂Cl₂) to afford1-[3-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]-3-(thiazol-2-yl)urea in(414 mg, 55%).

LC-MS (m/z): 379 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.72 (s, 3H), 6.44 (d, J=8.4 Hz, 1H),6.69-6.84 (m, 4H), 7.01-7.12 (m, 2H), 7.35-7.36 (d, J=4.0 Hz, 1H), 8.28(br, 1H), 10.28 (br, 1H).

Example 70N-[2-(2,3-Dimethoxyphenoxy)-5-methoxyphenyl]-N′-thiazol-2-ylurea

2-(2,3-Dimethoxyphenoxy)-5-methoxy-1-nitrobenzene (0.85 g, 56%) wasprepared from 2,3-dim ethoxyphenol (0.85 g, 5.5 mmol) and4-chloro-3-nitroanisole (0.94 g, 5.0 mmol) following the generalprocedure A. This was reduced to2-(2,3-dimethoxyphenoxy)-5-methoxyaniline (0.65 g, 85%) followinggeneral procedure C.N-[2-(2,3-Dimethoxyphenoxy)-5-methoxyphenyl]-N′-(thiazol-2-yl)urea (124g, 62%) was prepared from 2-(2,3-dimethoxy-phenoxy)-5-methoxyaniline(133 mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 403 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.70 (s, 3H), 3.79 (s, 3H), 3.87 (s,3H), 6.53-6.57 (m, 2H), 6.75 (d, J=8.8 Hz, 1H), 6.85 (dd, J=8.4, 1.2 Hz,1H), 7.00 (d, J=8.4 Hz, 1H), 7.04 (d, J=3.6 Hz, 1H), 7.30 (d, J=3.6 Hz,1H), 8.10 (d, J=3.6 Hz, 1H), 10.26 (br, 1H).

Example 71N-[2-(2,3-Dimethoxyphenoxy)-4-methylphenyl]-N′-(thiazol-2-yl)urea

3-(2,3-Dimethoxyphenoxy)-4-nitrotoluene (0.92 g, 64%) was prepared from2,3-di-methoxyphenol (0.85 g, 5.5 mmol) and 3-fluoro-4-nitrotoluene(0.78 g, 5.0 mmol) following the general procedure A. This was reducedto 2-(2,3-dimethoxyphenoxy)-4-methylaniline (0.65 g, 79%) followinggeneral procedure C.N-[2-(2,3-Dimethoxyphenoxy)-4-methylphenyl]-N′-(thiazol-2-yl)urea (120mg, 63%) was prepared from 2-(2,3-dimethoxyphenoxy)-4-methyl-aniline(130 mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 387 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 2.20 (s, 3H), 3.67 (s, 3H), 3.88 (s, 3H)6.57 (d, J=1.2 Hz, 1H), 6.64 (dd, J=8.4, 1.6 Hz, 1H), 6.89-6.92 (m, 2H),7.01-7.08 (m, 2H), 7.31 (d, J=3.6 Hz, 1H), 8.24 (d, J=8.4 Hz, 1H), 8.60(br, 1H), 10.23 (br, 1H).

Example 72N-[2-(2,3-Dimethoxyphenoxy)-3-methylphenyl]-N′-(thiazol-2-yl)urea

2-(2,3-Dimethoxyphenoxy)-3-nitrotoluene (0.80 g, 56%) was prepared from2,3-dimethoxyphenol (0.85 g, 5.5 mmol) and 2-chloro-3-nitrotoluene (0.85g, 5.0 mmol) following the general procedure A. This was reduced to2-(2,3-dimethoxyphenoxy)-3-methylaniline (0.54 g, 76%) following generalprocedure C.N-[2-(2,3-Dimethoxyphenoxy)-3-methylphenyl]-N′-(thiazol-2-yl)urea (116mg, 61%) was prepared from 2-(2,3-dimethoxyphenoxy)-3-methyl-aniline(130 mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 387 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 2.09 (s, 3H), 3.88 (s, 6H), 6.07 (dd,J=8.4, 1.2 Hz, 1H), 6.73 (dd, J=8.4, 1.2 Hz, 1H), 6.85-6.89 (m, 1H),6.98-7.00 (m, 2H), 7.16-7.20 (m, 1H), 7.24 (d, J=3.6 Hz, 1H), 8.27 (d,J=8.0 Hz, 1H), 8.95 (br, 1H), 10.09 (br, 1H).

Example 73 N-[2-(2-Chlorophenoxy)-5-chlorophenyl]-N′-(thiazol-2-yl)urea

N-[2-(2-Chlorophenoxy)-5-chlorophenyl]-N′-(thiazol-2-yl)urea (119 mg,63%) was prepared from 2-(2-chlorophenoxy)-5-chloroaniline (127 mg, 0.5mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 381 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.76 (d, J=8.4 Hz, 1H), 7.04 (dd, J=8.4,2.4 Hz, 1H), 7.07 (d, J=3.6 Hz, 1H), 7.17 (d, J=8.4 Hz, 1H), 7.24-7.42(m, 3H), 7.59 (dd, J=8.0, 1.6 Hz, 1H), 8.55 (d, J=2.4 Hz, 1H), 9.01 (br,1H), 10.28 (br, 1H).

Example 74N-[5-Chloro-2-(4-chloro-3-methylphenoxy)phenyl]-N′-(thiazol-2-yl)urea

N-[5-Chloro-2-(4-chloro-3-methylphenoxy)phenyl]-N′-(thiazol-2-yl)urea(236 mg, 60%) was prepared from2-(2-methyl-3-chlorophenoxy)-5-chloroaniline (commercially available,268 mg, 1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following thegeneral procedure D.

LC-MS (m/z): 397 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 2.35 (s, 3H), 6.90-7.02 (m, 2H),7.06-7.10 (m, 3H), 7.32 (d, J=3.6 Hz, 1H), 7.40 (d, J=8.8 Hz, 1H), 8.54(d, J=2.4 Hz, 1H), 10.22 (br, 2H).

Example 75N-[2-(4-Chlorophenoxy)-5-(trifluoromethyl)phenyl]-N′-(thiazol-2-yl)urea

N-[2-(4-Chlorophenoxy)-5-(trifluoromethyl)phenyl]-N′-(thiazol-2-yl)urea(136 mg, 66%) was prepared from2-(4-Chlorophenoxy)-5-(trifluoromethyl)aniline (144 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 415 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 5.12 (br, 1H), 7.02 (d, J=9 Hz, 1H),7.09 (d, J=3.6 Hz, 1H), 7.21 (d, J=8.8 Hz, 2H), 7.34 (d, J=3.6 Hz, 1H),7.39 (d, J=8.8 Hz, 1H), 7.49 (d, J=8.8 Hz, 2H), 8.85 (d, J=1.5 Hz, 1H),8.95 (br, 1H), 10.29 (br, 1H).

Example 76N-[4,5-difluoro-2-(2,3-dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

4,5-Difluoro-2-(2,3-dimethoxyphenoxy)-1-nitrobenzene (1.4 g, 90.3%) wasprepared from 2,3-dimethoxyphenol (0.85 g, 5.5 mmol) and1,3,4-trifluoronitrobenzene (0.885 g, 5.0 mmol) following the generalprocedure F. The product was then reduced to2-(2-methoxy-phenoxy)-4,5-difluoroaniline (1.35 g, 96.1%) followinggeneral procedure B.N-[4,5-Difluoro-2-(2,3-dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea(0.181 g, 89%) was prepared from2-(2,3-dimethoxyphenoxy)-4,5-difluoroaniline (0.140 g, 0.5 mmol) and2-aminothiazole (0.060 g, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 361 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.71 (s, 3H), 3.88 (s, 3H), 6.63 (dd,J=1.6, 8.4 Hz, 1H), 6.89 (dd, J=1.2, 6.4 Hz, 1H), 7.03-7.11 (m, 2H),7.38 (d, J=3.6 Hz, 1H), 8.26 (dd, J=1.6 Hz, 7.6 Hz, 1H), 8.42 (dd, J=1.2Hz, 7.2 Hz, 1H), 9.13 (br, 1H), 10.22 (br, 1H).

Example 77N-[4,5-Dichloro-2-(2,3-dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea

4,5-Dichloro-2-(2,3-dimethoxyphenoxy)-1-nitrobenzene (1.12 g, 65%) wasprepared from 2,3-dimethoxyphenol (0.85 g, 5.5 mmol) and4,5-dichloro-2-fluoro-1-nitrobenzene (1.05 g, 5.0 mmol) following thegeneral procedure A. This was reduced to4,5-dichloro-2-(2,3-di-methoxyphenoxy)aniline (0.68 g, 67%) followinggeneral procedure B.N-[4,5-Dichloro-2-(2,3-dimethoxyphenoxy)phenyl]-N′-(thiazol-2-yl)urea(136 mg, 62%) was prepared from4,5-di-chloro-2-(2,3-dimethoxyphenoxy)aniline (157 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 441 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.70 (s, 3H), 3.91 (s, 3H), 6.81-6.83(m, 2H), 7.01 (dd, J=8.4, 1.2 Hz, 1H), 7.09 (d, J=3.6 Hz, 1H), 7.15 (t,J=8.4 Hz, 1H), 7.34 (d, J=3.6 Hz, 1H), 8.65 (s, 1H), 8.95 (br, 1H),10.36 (br, 1H).

Example 78N-[5-Chloro-2-(2,3-dimethoxyphenoxy)-4-dimethylaminophenyl]-N′-(thiazol-2-yl)urea

4,5-Dichloro-2-(2,3-dimethoxyphenoxy)-1-nitrobenzene (0.35 g, 1.0 mmol)was heated with dimethylamine in tetrahydrofuran (4 ml, 2 M) in a sealedvial at 80° C. for 48 h. The reaction mixture was cooled to roomtemperature and dissolved in ethyl acetate (15 ml). The solution waswashed (water, brine) and concentrated to obtain the desirednitrobenzene, which was reduced to5-chloro-2-(2,3-dimethoxyphenoxy)-4-(dimethylamino)aniline (0.23 g, 73%)following general procedure B.N-[5-Chloro-2-(2,3-dimethoxyphenoxy)-4-dimethyl-aminophenyl]-N′-(thiazol-2-yl)urea(136 mg, 61%) was prepared from5-chloro-2-(2,3-di-methoxyphenoxy)-4-(dimethylamino)aniline (161 mg, 0.5mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 450 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 2.61 (s, 3H), 2.66 (s, 3H), 3.70 (s,3H), 3.89 (s, 3H), 6.58 (s, 1H), 6.68 (dd, J=8.4, 1.2 Hz, 1H), 6.92 (dd,J=8.4, 1.6 Hz, 1H), 7.04-7.10 (m, 2H), 8.44 (s, 1H), 9.20 (br, 1H),10.26 (br, 1H).

Example 79N-[5-Chloro-2-(2,3-dimethoxyphenoxy)-4-(4-morpholino)phenyl]-N′-(thiazol-2-yl)urea

4,5-Dichloro-2-(2,3-dimethoxyphenoxy)-1-nitrobenzene (0.35 g, 1.0 mmol)was heated with morpholine (4 ml) in a sealed vial at 100° C. for 48 h.The reaction mixture was cooled to rt and dissolved in ethyl acetate (15ml). The solution was washed (water, brine) and concentrated to obtainthe desired nitrobenzene, which was reduced to5-chloro-2-(2,3-dimethoxyphenoxy)-4-(4-morpholino)aniline (0.22 g, 61%)following general procedure B.N-[5-Chloro-2-(2,3-dimethoxyphenoxy)-4-(4-morpholino)phenyl]-N′-(thiazol-2-yl)urea(127 mg, 52%) was prepared from5-chloro-2-(2,3-dimethoxyphenoxy)-4-(4-morpholino)aniline (182 mg, 0.5mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 492 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 2.83 (m, 4H), 3.69-3.72 (m, 7H), 3.89(s, 3H), 6.58 (s, 1H), 6.69 (dd, J=8.4, 1.6 Hz, 1H), 6.93 (dd, J=8.4,1.6 Hz, 1H), 7.05-7.10 (m, 2H), 7.31 (d, J=3.2 Hz, 1H), 8.48 (s, 1H),9.02 (br, 1H), 10.25 (s, 1H).

Example 80 N-[2-(2,4-Difluorophenoxy)pyridin-3-yl]-N′-(thiazol-2-yl)urea

N-2-(2,4-Difluorophenoxy)pyridin-3-yl-N′-(thiazol-2-yl)urea (112 mg,65%) was prepared from 3-amino-2-(2,4-difluorophenoxy)pyridine (111 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 350 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 7.08-7.16 (m, 3H), 7.20-7.26 (m, 1H),7.36 (d, J=3.2 Hz, 1H), 7.40-7.46 (m, 1H), 7.71 (dd, J=4.8, 1.6 Hz, 1H),8.69 (dd, J=8.0, 1.6 Hz, 1H), 9.00 (br, 1H), 10.31 (br, 1H).

Example 81 N-[2-(2-Fluorophenoxy)pyridin-3-yl]-N′-[thiazol-2-yl]urea

N-2-(2-Fluorophenoxy)pyridin-3-yl-N′-(thiazol-2-yl)urea (112 mg, 68%)was prepared from 3-amino-2-(2-fluorophenoxy)pyridine (102 mg, 0.5 mmol)and 2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 332 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 7.09 (d, J=3.6 Hz, 1H) 7.13 (dd, J=8.0,4.8 Hz, 1H), 7.25-7.39 (m, 5H), 7.71 (dd, J=4.8, 1.6 Hz, 1H), 8.69 (dd,J=8.4, 1.6 Hz, 1H), 9.00 (br, 1H), 10.31 (br, 1H).

Example 82 N-[2-(2-Methoxyphenoxy)pyridin-3-yl]-N′-(thiazol-2-yl)urea

2-(2-Methoxy)phenoxy-3-nitropyridine (0.86 g, 70%) was prepared from2-methoxy-phenol (0.68 g, 5.5 mmol) and 2-bromo-3-nitropyridine (1.05 g,5.0 mmol) following the general procedure A. This compound was reducedto 2-(2-methoxyphenoxy)-3-amino-pyridine (0.49 g, 65%) following generalprocedure B. N-[2-(2-Methoxyphenoxy)pyridin-3-yl]-N′-(thiazol-2-yl)urea(126 g, 74%) was prepared from 2-(2-methoxyphenoxy)-3-aminopyridine (108mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 344 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.69 (s, 3H), 6.74 (d, J=3.6 Hz, 1H),6.99-7.01 (m, 2H), 7.16-7.21 (m, 3H), 7.45 (d, J=2.8 Hz, 1H), 7.71 (d,J=4.0 Hz, 1H), 8.57-8.59 (d, J=8.0 Hz, 1H), 8.89 (br, 1H), 10.44 (br,1H).

Example 83 N-[2-(2,3-Dimethoxyphenoxy)pyridin-3-yl]-N-(thiazol-2-yl)urea

2-(2,3-Dimethoxy)phenoxy-3-nitropyridine (1.03 g, 75%) was prepared from2,3-dimethoxyphenol (0.85 g, 5.5 mmol) and 2-bromo-3-nitropyridine (1.05g, 5.0 mmol) following the general procedure A. This compound wasreduced to 2-(2,3-dimethoxyphenoxy)-3-aminopyridine (0.57 g, 62%)following the general procedure B.N-[2-(2,3-Dimethoxy-phenoxy)pyridin-3-yl]-N′-(thiazol-2-yl)urea (131 mg,70%) was prepared from 2-(2,3-di-methoxyphenoxy)-3-aminopyridine (123mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 374 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.58 (s, 3H), 3.87 (s, 3H), 6.81 (dd,J=1.6, 8.0 Hz, 1H), 6.95 (dd, J=1.6, 8.4 Hz, 1H), 7.05-7.07 (m, 3H),7.35 (d, J=3.2 Hz, 1H), 7.67-7.79 (m, 1H), 8.64-8.86 (dd, J=2.4, 8.0 Hz,1H), 8.89 (br, 1H), 10.26 (br, 1H).

Example 84 N-[4-Chloro-2-(2-chlorobenzoyl)phenyl]-N′-(thiazol-2-yl)urea

N-[4-Chloro-2-(2-chlorobenzoyl)phenyl]-N′-(thiazol-2-yl)urea (0.51 g,86%) was prepared from 2-amino-2′,5-dichlorobenzophenone (0.4 g, 1.50mmol) and 2-aminothiazole (150 mg, 1.5 mmol) following the generalprocedure D.

LC-MS (m/z): 394 (M+1), ¹H NMR (400 MHz, CDCl₃): δ 6.45 (br, 1H), 6.79(dd, J=1.2, 7.6 Hz, 2H), 7.11 (d, J=7.2 Hz, 1H), 7.25-7.49 (m, 1H),6.91-7.33 (m, 3H), 8.65 (d, J=8.8 Hz, 1H), 8.68 (d, J=9.6 Hz, 1H), 8.93(br, 1H).

Example 85 N-[4-Chloro-2-(2-fluorobenzoyl)phenyl]-N′-(thiazol-2-yl)urea

N-[4-Chloro-2-(2-fluorobenzoyl)phenyl]-N′-(thiazol-2-yl)urea (116 mg,62%) was prepared from 2-amino-5-chloro-2′-fluorobenzophenone (125 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 377 (M+1)⁺.

Example 86N-[2-(2,4-Difluorophenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea

2-(2,4-Difluorophenylsulfanyl)-1-nitrobenzene (1.04 g, 78%) was preparedfrom 2,4-difluorothiophenol (0.73 g, 5.5 mmol) and 2-fluoronitrobenzene(0.71 g, 5.0 mmol) following the general procedure A. This compound wasreduced to 2-(2,4-difluorophenylsulfanyl)-aniline (0.64 g, 70%)following the general procedure B.1-[2-(2,4-Difluorophenylsulfanyl)-phenyl]-3-(thiazol-2-yl)urea (130 g,72%) was prepared from 2-(2,4-difluorophenylsulfanyl)-aniline (118 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 365 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.69-6.79 (m, 3H), 6.85 (d, J=3.6 Hz,1H), 7.04-7.09 (m, 1H), 7.36-7.40 (m 2H), 7.51-7.53 (dd, J=1.6, 8.0 Hz,1H), 8.42 (d, J=8.0 Hz, 1H), 8.88 (br, 1H), 10.2 (br, 1H).

Example 87 1-[2-(2-Fluorophenylsulfanyl)phenyl]-3-(thiazol-2-yl)urea

2-(2-Fluorophenylsulfanyl)nitrobenzene (1.03 g, 83%) was prepared from2-fluoro-thiophenol (0.70 g, 5.5 mmol) and 2-fluoronitrobenzene (0.71 g,5.0 mmol) following the general procedure A. This compound was reducedto 2-(2-fluorophenylsulfanyl)aniline (0.65 g, 72%) following generalprocedure B. N-[2-(2-Fluorophenylsulfanyl)phenyl]-N′-(thiazol-2-yl)-urea(129 mg, 75%) was prepared from 2-(2-fluorophenylsulfanyl)aniline (107mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 347 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.74-6.82 (m, 1H), 7.02-7.07 (m, 2H),7.14-7.23 (m, 3H), 7.29 (d, J=3.6 Hz, 1H), 7.51-7.58 (m, 1H), 7.60 (dd,J=1.2, 7.6 Hz, 1H), 8.43-8.46 (d, J=8.8 Hz, 1H), 9.08 (br, 1H), 10.39(br, 1H).

Example 88N-[2-(2-Chloro-4-fluorophenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea

2-(2-Chloro-4-fluorophenylsulfanyl)nitrobenzene (1.13 g, 80%) wasprepared from 2-chloro-4-fluorothiophenol (0.89 g, 5.5 mmol) and2-fluoronitrobenzene (0.71 g, 5.0 mmol) following the general procedureA. This compound was reduced to2-(2-chloro-4-fluoro-phenylsulfanyl)aniline (0.76 g, 75%) following thegeneral procedure B.N-[2-(2-Chloro-4-fluorophenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea (144mg, 76%) was prepared from 2-(2-chloro-4-fluorophenylsulfanyl)aniline(126 mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 381 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 6.59-6.68 (m, 1H), 6.96-7.04 (m, 2H),7.16-7.22 (m, 1H), 7.26 (d, J=4.0 Hz, 1H), 7.32-7.38 (m, 1H), 7.50-7.61(m, 2H), 8.47 (d, J=8.0 Hz, 1H), 9.00 (br, 1H), 10.23 (br, 1H).

Example 89N-[2-(2,3-Dichlorophenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea

2-(2,3-Dichlorophenylsulfanyl)nitrobenzene (1.25 g, 84%) was preparedfrom 2,3-dichlorothiophenol (0.97 g, 5.5 mmol) and 2-fluoronitrobenzene(0.71 g, 5.0 mmol) following the general procedure A. This compound wasreduced to 2-(2,4-dichlorophenylsulfanyl)-aniline (0.81 g, 72%)following the general procedure B.N-[2-(2,3-Dichlorophenylsulfanyl)-phenyl]-N′-(thiazol-2-yl)urea (154 mg,78%) was prepared from 2-(2,3-chlorophenylsulfanyl)-aniline (135 mg, 0.5mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 397 (M+1)⁺.

¹H NMR (400 MHz, CDCl₃): δ 6.34-6.44 (m, 1H), 6.72-6.78 (m, 1H),6.88-6.96 (m, 1H), 7.11-7.22 (m, 3H), 7.50-7.57 (m, 2H), 8.51-8.53 (d,J=6.0 Hz, 1H), 9.08 (br, 1H), 10.32 (br, 1H).

Example 90N-[2-(3,5-Dimethylphenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea

2-(3,5-Dimethylphenylsulfanyl)nitrobenzene (1.01 g, 78%) was preparedfrom 3,5-dimethylthiophenol (0.76 g, 5.5 mmol) and 2-fluoronitrobenzene(0.71 g, 5.0 mmol) following the general procedure A. This compound wasreduced to 2-(3,5-dimethylphenylsulfanyl)-aniline (0.64 g, 72%)following the general procedure B.N-[2-(3,5-Dimethylphenylsulfanyl)-phenyl]-N′-(thiazol-2-yl)urea (131 mg,74%) was prepared from 2-(3,5-dimethylphenyl-sulfanyl)aniline (115 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 357 (M+1)⁺.

¹H NMR (400 MHz, CDCl₃): δ 2.09 (s, 6H), 6.54-6.86 (m, 4H), 7.04-7.10(m, 1H), 7.27-7.34 (m, 1H), 7.41-7.46 (m, 1H), 7.48-7.56 (bs, 1H), 8.41(d, J=8.4 Hz, 1H), 8.20 (br, 1H), 11.8 (br, 1H).

Example 91N-[2-(2-Methoxycarbonylphenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea

2-(2-Methoxycarbonylphenylsulfanyl)nitrobenzene (1.15 g, 80%) wasprepared from methyl thiosalicylate (0.92 g, 5.5 mmol) and2-fluoronitrobenzene (0.71 g, 5.0 mmol) following the general procedureA. This compound was reduced to2-(2-methoxycarbonyl-phenylsulfanyl)aniline (0.75 g, 73%) following thegeneral procedure B.N-[2-(2-Methoxy-carbonylphenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea(142 mg, 74%) was prepared from2-(2-methoxycarbonylphenylsulfanyl)aniline (130 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 387 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.88 (s, 3H), 6.62-6.82 (m, 2H),7.02-7.24 (m, 4H), 7.44-7.50 (m, 1H), 7.55-7.64 (bs, 1H), 7.87 (d,J=6.4, 1H), 8.42 (d, J=8.0 Hz, 1H), 8.82 (br, 1H), 10.9 (br. 1H).

Example 92 N-[2-(2-Methoxyphenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea

2-(2-Methoxyphenylsulfanyl)nitrobenzene (1.07 g, 82%) was prepared from2-methoxy thiophenol (0.76 g, 5.5 mmol) and 2-fluoronitrobenzene (0.71g, 5.0 mmol) following the general procedure A. This compound wasreduced to 2-(2-methoxyphenylsulfanyl)aniline (0.66 g, 70%) followinggeneral procedure B.N-[2-(2-Methoxyphenylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea (110 mg,62%) was prepared from 2-(2-methoxyphenylsulfanyl)aniline (115 mg, 0.5mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 359 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.48 (s, 3H), 6.77-6.89 (m, 2H),6.90-7.00 (m, 2H), 7.05-7.24 (m, 2H), 7.29 (d, J=3.6 Hz, 1H), 7.38-7.42(m, 1H), 7.55 (dd, J=1.6, 8.0 Hz, 1H), 8.41-8.43 (d, J=8.4 Hz, 1H), 8.89(br, 1H), 10.22 (br, 1H).

Example 93 N-[2-(2-Pyridinylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea

2-(2-Pyridylsulfanyl)nitrobenzene (0.70 g, 60%) was prepared from2-mercapto-pyridine (0.61 g, 5.5 mmol) and 2-fluoronitrobenzene (0.71 g,5.0 mmol) following the general procedure A. This compound was reducedto 2-(2-pyridylsulfanyl)aniline (0.37 g, 62%) following generalprocedure B. N-[2-(2-Pyridylsulfanyl)phenyl]-N′-(thiazol-2-yl)urea (98mg, 60%) was prepared from 2-(2-pyridylsulfanyl)aniline (101 mg, 0.5mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 330 (M+1)⁺.

¹H NMR (400 MHz, CDCl₃): δ 6.78-6.80 (d, J=8.0 Hz, 1H), 6.96 (d, J=3.6Hz, 1H), 7.03-7.07 (m, 1H), 7.13-7.18 (m, 1H), 7.23 (d, J=2.8 Hz, 1H),7.51-7.57 (m, 2H), 7.64 (d, J=1.6, 7.6 Hz, 1H), 8.35 (d, J=4.0 Hz, 1H),8.45 (d, J=8.4 Hz, 1H), 8.13 (br, 1H), 10.44 (br, 1H).

Example 94 N-(2-Propyloxyphenyl)-N′-(thiazol-2-yl)urea

N-(2-Propyloxyphenyl)-N′-(thiazol-2-yl)urea (97 mg, 70%) was preparedfrom 2-propyloxyaniline (76 mg, 0.5 mmol) and 2-aminothiazole (60 mg,0.6 mmol) following the general procedure D.

LC-MS (m/z): 279 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 1.07 (t, J=7.6 Hz, 3H), 1.88 (m, 2H),4.05 (q, J=7.6 Hz), 6.90-7.01 (m, 3H), 7.05 (d, J=3.6 Hz), 7.36 (d,J=3.6 Hz), 8.30 (dd, J=7.6, 1.6 Hz, 1H), 8.80 (br, 1H), 10.24 (br, 1H).

Example 95 N-(2-Butyloxyphenyl)-N′-(thiazol-2-yl)urea

N-(2-Butyloxyphenyl)-N′-(thiazol-2-yl)urea (94 mg, 65%) was preparedfrom 2-butylyloxyaniline (82 mg, 0.5 mmol) and 2-aminothiazole (60 mg,0.6 mmol) following the general procedure D.

LC-MS (m/z): 293 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 0.98 (t, J=7.2 Hz, 3H), 1.54 (m, 2H),1.84 (quint, J=6.4 Hz, 2H), 4.10 (t, J=6.4 Hz, 2H), 6.90-7.03 (m, 3H),7.05 (d, J=3.6 Hz, 1H), 7.25 (d, J=3.6 Hz, 1H), 8.30 (dd, J=8.0, 1.2 Hz,1H), 9.00 (br, 1H), 10.20 (br, 1H).

Example 96 N-(2-(Cyclopentyloxyphenyl)-N′-(thiazol-2-yl)urea

2-(Cyclopentyloxy)-1-nitrobenzene (1.04 g, 80%) was prepared fromcyclopentanol (0.46 ml, 5.0 mmol) and 1-fluoro-2-nitrobenzene (0.71 g,5.0 mmol) following the general procedure G. This was reduced to2-(cyclopentyloxy)aniline (0.30 g, 68%, 2.5 mmol scale) followinggeneral procedure B. N-(2-Cyclopentyloxyphenyl)-N′-(thiazol-2-yl)urea(212 mg, 70%) was prepared from 2-(cyclopentyloxy)aniline (177 mg, 1.0mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following the generalprocedure D.

LC-MS (m/z): 305 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 1.60-2.05 (m, 8H), 4.94 (m, 1H),6.90-7.05 (m, 4H), 7.35 (d, J=4.0 Hz, 1H), 8.30 (d, J=8.8 Hz, 1H), 10.20(br, 2H).

Example 97 N-(2-Isopropoxyphenyl)-N′-(thiazol-2-yl)urea

2-(Isopropoxy)-1-nitrobenzene (317 mg, 70%) was prepared from isopropylalcohol (0.24 ml, 3.0 mmol) and 1-fluoro-2-nitrobenzene (0.36 g, 2.5mmol) following the general procedure G. This was reduced to2-(isopropoxy)aniline (198 mg, 75%) following general procedure B.N-(2-Isopropoxyphenyl)-N′-thiazolylurea (218 mg, 60%) was prepared from2-(isopropoxy)aniline (198 mg, 01.3 mmol) and 2-aminothiazole (150 mg,1.5 mmol) following the general procedure D.

LC-MS (m/z): 279 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 1.36 (d, J=6.4 Hz, 6H), 4.71 (m, 1H),6.90-7.07 (m, 4H), 7.36 (d, J=3.6 Hz, 1H), 8.30 (d, J=8.0 Hz, 1H), 10.22(br, 2H)

Example 98 N-[2-(2-Methylpropoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2-Methylpropoxy)-1-nitrobenzene (0.73 g, 75%) was prepared from2-methyl-propanol (0.46 ml, 5.0 mmol) and 1-fluoro-2-nitrobenzene (0.71g, 5.0 mmol) following the general procedure G. This was reduced to2-(2-methylpropoxy)aniline (0.29 g, 70%, 2.5 mmol scale) followinggeneral procedure B.N-[2-(2-Methylpropoxy)phenyl]-N′-(thiazol-2-yl)-urea (189 mg, 65%) wasprepared from 2-(2-methylpropoxy)aniline (165 mg, 1.0 mmol) and2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

LC-MS (m/z): 293 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 1.09 (d, 6H), 2.13 (m, 1H), 3.86 (d,J=6.8 Hz, 1H), 6.90-7.10 (m, 4H), 7.38 (d, J=3.6 Hz, 1H), 8.29 (d, J=7.2Hz, 1H), 10.05 (br, 2H).

Example 99 N-[2-(Cyclopentylmethoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(Cyclopentylmethoxy)-1-nitrobenzene (443 mg, 80%) was prepared fromcyclo-pentanemethanol (0.32 ml, 3.0 mmol) and 1-fluoro-2-nitrobenzene(0.36 g, 2.5 mmol) following the general procedure G. This was reducedto 2-(cyclopentylmethoxy)aniline (268 mg, 70%) following generalprocedure B. N-[2-(Cyclopentylmethoxy)phenyl]-N′-(thiazol-2-yl)-urea(286 mg, 60%) was prepared from 2-(cyclopentylmethoxy)aniline (0.25 g,1.5 mmol) and 2-aminothiazole (150 mg, 1.5 mmol) following the generalprocedure D.

LC-MS (m/z): 319 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 1.40 (m, 2H), 1.65 (m, 4H), 1.91 (m,2H), 2.45 (m, 1H), 3.98 (d, J=7.6 Hz, 1H), 6.88-7.06 (m, 4H), 7.35 (d,J=3.6 Hz, 1H), 8.29 (d, J=7.6 Hz, 1H), 10.14, (br, 2H).

Example 100 N-[2-(3-pentoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(3-Pentoxy)-1-nitrobenzene (366 mg, 70%) was prepared from 3-pentanol(0.27 ml, 2.5 mmol) and 1-fluoro-2-nitrobenzene (0.36 g, 2.5 mmol)following the general procedure G. This was reduced to2-(3-pentoxy)aniline (0.25 g, 80%) following general procedure B.N-[2-(3-pentoxy)phenyl]-N′-(thiazol-2-yl)urea (0.26 g, 57%) was preparedfrom 2-(3-pentoxy)-aniline (0.25 g, 1.5 mmol) and 2-aminothiazole (150mg, 1.5 mmol) following the general procedure D.

LC-MS (m/z): 307 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 0.92 (t, J=7.2 Hz, 6H), 1.75 (m, 4H),4.38 (m, 1H), 6.89-7.06 (m, 4H), 7.36 (d, J=3.6 Hz, 1H), 8.32 (d, J=8.0Hz, 1H).

Example 101 N-[2-(2-pentoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2-Pentoxy)-1-nitrobenzene (387 mg, 74%) was prepared from 2-pentanol(0.27 ml, 2.5 mmol) and 1-fluoro-2-nitrobenzene (0.36 g, 2.5 mmol)following the general procedure G. This was reduced to2-(2-pentoxy)aniline (0.26 g, 79%) following general procedure B.N-[2-(2-pentoxy)phenyl]-N′-(thiazol-2-yl)urea (280 mg, 62%) was preparedfrom 2-(2-pentoxy)aniline (0.25 g, 1.5 mmol) and 2-aminothiazole (150mg, 1.5 mmol) following the general procedure D:

LC-MS (m/z): 307 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 0.93 (t, J=7.2 Hz, 3H), 1.32 (d, J=6.0Hz, 3H), 1.40-1.90 (m, 4H), 4.55 (m, 1H), 6.85-7.07 (m, 4H), 7.36 (d,J=3.6 Hz, 1H), 8.31 (d, J=8.0 Hz, 1H), 10.15 (br, 1H).

Example 102 N-[2-(2-Methoxyethoxy)phenyl]-N′-(thiazol-2-yl)urea

2-(2-Methoxyethoxy)-1-nitrobenzene (0.25 g, 64%) was prepared from2-methoxy-ethanol (0.16 ml, 2.0 mmol) and 1-fluoro-2-nitrobenzene (0.21ml, 2.0 mmol) following the general procedure G. This was reduced to2-(2-methoxyethoxy)aniline (0.13 g, 60%) following general procedure B.N-[2-(2-Methoxyethoxy)phenyl]-N′-(thiazol-2-yl)urea (115 mg, 55%) wasprepared from 2-(2-methoxyethoxy)aniline (115 mg, 0.7 mmol) and2-amino-thiazole (140 mg, 1.4 mmol) following the general procedure D.

LC-MS (m/z): 295 (M+1)⁺.

¹H NMR (400 MHz, acetone-d₆): δ 3.37 (s, 3H), 3.78 (t, J=4.8 Hz, 2H),4.25 (t, J=4.8 Hz, 2H), 6.95-7.06 (m, 4H), 7.37 (d, J=3.6 Hz, 1H), 8.29(d, J=8.0 Hz, 1H), 8.80 (br, 1H), 10.20 (br, 1H).

Example 103 General Procedure (H)(2-[3-(2-Benzylphenyl)ureido]thiazol-4-yl)acetic acid

The intermediate 2-benzylphenyl isocyanate (0.26 g, 1.2 mmol) (generalprocedure H2) was dissolved in DMF (5 ml) and 2-amino-4-thiazole aceticacid (0.20 g, 1.2 mmol) was added. After 16 hours at 20° C. ethylacetate(60 ml) was added and the mixture was extracted with water (5×20 ml).The solvent was removed in vacuo and the remaining oil was purified onWaters Deltprep 4000 giving 150 mg of the title compound.

Preparative system: (gradient 20-90% CH₃CN 40 min., 20 ml/min., Rt=35min Solvent A=water, solvent B=CH₃CN, solvent C=0.5% TFA/water).

¹H-NMR (DMSO-d₆): δ 10.90 (broad, 1H); 8.45 (s, 1H); 7.80 (s, 1H); 7.20(multi, 9H); 6.85 (s, 1H); 3.98 (s, 2H); 3.53 (s, 2H).

HPLC-MS (Method A): m/z=368 (M+1); R_(t)=4.10 min

¹H NMR (CDCl₃): δ 7.98 (br d, 2H), 7.88-7.70 (m, 4H), 7.50 (t, 3H), 7.18(d, 1H), 6.84 (br s, 1H), 3.71 (br s, 2H), 2.70 (br s, 2H), 2.52 (m,1H), 1.90-1.70 (m, 5H), 1.45-1.15 (m, 5H).

Example 104 General Procedure (H)(2-[3-(2-Benzoyl-4-chlorophenyl)ureido]thiazol-4-yl)acetic acid

The title compound was prepared as in example 103 using(5-chloro-2-isocyanato-phenyl)phenyl methanone (general procedure H2) asintermediate isocyanate.

¹H-NMR (DMSO-d₆): Selected data: δ 9.48 (broad, 1H); 8.12 (broad, 1H);(multi, 9H); 6.87 (s, 1H); 3.57 (s, 2H).

HPLC-MS (method A): m/z=415 (M+1); R_(t)=3.79 min

Example 105 General Procedure (H)(2-[3-(2-(2-Methylphenoxy)phenyl)ureido]thiazol-4-yl)acetic acid

The title compound was prepared as in example 103 using2-(2-methylphenoxy)-phenyl isocyanate (general procedure H2) asintermediate isocyanate.

¹H-NMR (DMSO-d₆): δ 11.09 (broad, 1H); 8.88 (broad, 1H); 8.25 (d, 1H);7.37 (d, 1H); 7.22 (t, 1H); 7.11 (multi, 2H); 6.97 (t, 1H); 6.89 (d,1H); 6.87 (s, 1H); 6.67 (d, 1H); 3.53 (s, 2H); 2.23 (s, 3H).

HPLC-MS (method A): m/z=384 (M+1); R_(t)=4.67 min

Example 106 General Procedure (H)(2-[3-(2-(4-Methoxyphenoxy)-5-(trifluoromethyl)phenyl)ureido]thiazol-4-yl)aceticacid

The title compound was prepared as in example 103 using2-(4-methoxyphenoxy)-5-(trifluoromethyl)phenyl isocyanate (generalprocedure H2) as intermediate isocyanate.

¹H-NMR (DMSO-d₆): δ 12.32 (broad, 1H); 11.20 (broad, 1H); 9.30 (d, 1H);8.62 (d, 1H); 7.32 (d, 1H); 7.17 (d, 2H); 7.05 (d, 2H); 6.90 (s, 1H);6.83 (d, 1H); 3.78 (s, 3H); 3.53 (s, 2H).

Example 107 General Procedure (H){2-[3-(2-phenoxyphenyl)ureido]thiazol-4-yl}acetic acid

The title compound was prepared as in example 103 using 2-phenoxyphenylisocyanate (general procedure H2) as intermediate isocyanate.

¹H NMR (CDCl₃) selected data: δ 3.47 (2H, s), 6.78 (1H, s), 6.90 (1H,d), 6.97-7.08 (3H, m), 7.09-7.19 (2H, m), 7.38 (2H, t), 8.16 (1H, br s),HPLC-MS (Method A): m/z=370 (M+1); R_(t)=3.50 min.

Example 108 General Procedure (H)2-{3-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazole-4-carboxylicacid

The title compound was prepared according to general procedure H.

¹H NMR (DMSO): δ 12.76 (br, 1H), 11.21 (br 1H), 9.23 (s, 1H), 8.06 (dd,1H), 7.94 (s, 1H), 7.33 (d, 1H), 7.10-7.01 (m, 2H), 6.74 (t, 1H), 6.55(dd, 1H), 3.80 (s, 3H).

HPLC-MS (Method B): m/z=422 (M+1); R_(t)=3.90 min.

Example 109 General Procedure (H)2-{3-[2-(2,3-Dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazole-4-carboxylicacid ethyl ester

¹H NMR (DMSO): δ 11.44 (s, 1H), 8.99 (s 1H), 8.06 (dd, 1H), 7.99 (s,1H), 7.09 (t, 1H), 6.94 (d, 1H), 6.80 (t, 1H), 6.72 (dd, 1H), 6.67 (d,1H), 4.25 (q, 2H), 3.84 (s, 3H), 3.67 (s, 3H), 1.28 (t, 3H).

HPLC-MS (Method B): m/z=462 (M+1); R_(t)=4.53 min.

Example 110 General Procedure (H)(2-{3-[2-(2,3-Dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazol-4-yl)aceticacid ethyl ester

¹H NMR (DMSO): δ 11.16 (br, 1H), 9.09 (br 1H), 8.08 (dd, 1H), 7.09 (t,1H), 6.94 (d, 1H), 6.92 (s, 1H), 6.78 (t, 1H), 6.70 (dd, 1H), 6.65 (d,1H), 4.06 (q, 2H), 3.84 (s, 3H), 3.66 (s, 2H), 3.62 (s, 3H), 1.18 (t,3H).

HPLC-MS (Method B): m/z=476 (M+1); R_(t)=4.43 min.

Example 111 General Procedure (H)(2-{3-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)aceticacid

¹H NMR (DMSO): δ 12.27 (br, 1H), 11.06 (br, 1H), 9.22 (br, 1H), 8.06(dd, 1H), 7.32 (dd, 1H), 7.08 (d, 1H), 7.03 (t, 1H), 6.90 (s, 1H),6.75-6.70 (m, 2H), 6.53 (dd, 1H), 3.79 (s, 3H), 3.55 (s, 2H).

HPLC-MS (Method B): m/z=436 (M+1); R_(t)=3.85 min.

Example 112 General Procedure (H)2-{3-[2-(2,3-Dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazole-4-carboxylicacid

¹H NMR (DMSO): δ 12.77 (br, 1H), 11.33 (s, 1H), 9.06 (s, 1H), 8.07 (dd,1H), 7.93 (s, 1H), δ 7.08 (d, 1H), 7.09 (t, 1H), 6.95 (dd, 1H), 6.80 (t,1H), 6.73-6.63 (m, 2H), 3.84 (s, 3H), 3.66 (s, 3H).

HPLC-MS (Method B): m/z=434 (M+1); R_(t)=3.92 min.

Example 113 General Procedure (H)(2-{3-[2-(2,3-Dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazol-4-yl)aceticacid

¹H NMR (DMSO): δ 12.30 (br, 1H), 11.14 (br, 1H), 9.08 (br 1H), 8.08 (dd,1H), 7.08 (t, 1H), 6.94 (d, 1H), 6.89 (s, 1H), 6.78 (t, 1H), 6.70 (dd,1H), 6.66 (dd, 1H), 3.84 (s, 3H), 3.66 (s, 3H), 3.54 (s, 2H).

HPLC-MS (Method B): m/z=448 (M+1); R_(t)=3.76 min.

Example 114 General Procedure (H)2-{3-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}-4-methylthiazole-5-carboxylicacid ethyl ester

¹H NMR (DMSO): δ 11.35 (s, 1H), 9.38 (br 1H), 8.05 (dd, 1H), 7.32 (dd,1H), 7.10-7.02 (m, 2H), 6.76 (t, 1H), 6.56 (dd, 1H), 4.24 (q, 2H), 3.79(s, 3H), 2.52 (s, 3H), 1.29 (t, 3H).

HPLC-MS (Method B): m/z=464 (M+1); R_(t)=4.91 min.

Example 115 General Procedure (H)2-{3-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}-4-methylthiazole-5-carboxylicacid

¹H NMR (DMSO): δ 12.79 (br, 1H), 11.29 (br, 1H), 9.38 (br 1H), 8.05 (dd,1H), 7.32 (dd, 1H), 7.10-7.01 (m, 2H), 6.75 (t, 1H), 6.54 (dd, 1H), 3.79(s, 3H), 2.51 (s, 2H).

HPLC-MS (Method B): m/z=436 (M+1); R_(t)=4.19 min.

Example 116 General Procedure (H1)N-Ethyl-2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)acetamide

¹H NMR (DMSO): δ 11.03 (s, 1H), 9.22 (br 1H), 8.06 (dd, 1H), 7.89 (t,1H), 7.32 (dd, 1H), 7.10-7.00 (m, 2H), 6.82 (s, 1H), 6.72 (t, 1H), 6.53(dd, 1H), 3.79 (s, 3H), 3.39 (s, 2H), 3.07 (q, 2H), 1.01 (t, 3H).

HPLC-MS (Method B): m/z=463 (M+1); R_(t)=4.06 min.

Example 117 General Procedure (H1)2-(2-{3-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)-N-(2-methoxy-ethyl)acetamide

¹H NMR (DMSO): δ 11.03 (br, 1H), 9.22 (br 1H), 8.06 (dd, 1H), 7.99 (t,1H), 7.32 (dd, 1H), 7.10-7.00 (m, 2H), 6.82 (s, 1H), 6.72 (t, 1H), 6.53(dd, 1H), 3.79 (s, 3H), 3.43 (s, 2H), 3.34 (t, 2H), 3.24 (s, 3H), 3.23(t, 2H).

HPLC-MS (Method B): m/z=493 (M+1); R_(t)=4.01 min.

Example 118 General Procedure (H1)2-(2-{3-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)-N-(2-morpholin-4-ylethyl)acetamide

¹H NMR (DMSO): selected data: δ 11.01 (br, 1H), 9.77 (br, 1H), 9.23 (br1H), 8.19 (br, 1H), 8.06 (dd, 1H), 7.32 (dd, 1H), 7.10-7.00 (m, 2H),6.88 (s, 1H), 6.72 (t, 1H), 6.53 (dd, 1H), 3.97 (m, 2H), 3.79 (s, 3H),3.64 (m, 2H), 3.47 (s, 2H).

HPLC-MS (Method B): m/z=548 (M+1); R_(t)=3.24 min.

Example 119 General Procedure (H1)[2-(2-{3-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)acetylamino]aceticacid methyl ester

¹H NMR (DMSO): Selected data δ 11.06 (br, 1H), 9.25 (br 1H), 8.34 (t,1H), 8.06 (dd, 1H), 7.31 (dd, 1H), 7.10-7.00 (m, 2H), 6.88 (s, 1H), 6.73(t, 1H), 6.53 (dd, 1H), 3.85 (d, 2H), 3.79 (s, 3H), 3.63 (s, 2H), 3.49(s, 2H).

HPLC-MS (Method B): m/z=507 (M+1); R_(t)=3.74 min.

Example 120 General Procedure (H1)2-{3-[2-(2,3-Dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazole-4-carboxylicacid (2-methoxyethyl)amide

¹H NMR (DMSO): Selected data 611.29 (s, 1H), 9.13 (s 1H), 8.08 (dd, 1H),7.78 (t, 1H), 7.73 (s, 1H), 7.09 (t, 1H), 6.95 (dd, 1H), 6.80 (t, 1H),6.71 (dd, 1H), 6.67 (dd, 1H), 3.84 (s, 3H), 3.67 (s, 3H), 3.26 (s, 3H).

HPLC-MS (Method B): m/z=491 (M+1); R_(t)=3.86 min.

Example 121 General Procedure (H1)[2-(2-{3-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazol-4-yl)acetylamino]aceticacid

¹H NMR (DMSO): δ 12.54 (br, 1H), 11.06 (br, 1H), 9.23 (br 1H), 8.21 (t,1H), 8.06 (dd, 1H), 7.31 (dd, 1H), 7.09-7.01 (m, 2H), 6.88 (s, 1H), 6.72(t, 1H), 6.53 (dd, 1H), 3.79 (s, 3H), 3.76 (s, 2H), 3.49 (s, 2H).

HPLC-MS (Method B): m/z=493 (M+1); R_(t)=3.47 min.

Example 122 General Procedure (H)2-{3-[2-(2,3-Dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazole-4-carboxylicacid ethylamide

¹H NMR (DMSO): δ 11.21 (s, 1H), 9.19 (s 1H), 8.08 (dd, 1H), 7.89 (t,1H), 7.69 (s, 1H), 7.10 (t, 1H), 6.95 (dd, 1H), 6.79 (t, 1H), 6.73-6.66(m, 2H), 3.84 (s, 3H), 3.66 (s, 3H), 3.25 (q, 2H), 1.08 (t, 3H). HPLC-MS(Method B): m/z = 461 (M + 1); R_(t) = 3.96 min. Microanalysis:Calculated for: C, 55.09%; H, 4.88%; N, 111.88%. Found: C, 55.18%; H,4.67%; N, 12.21%.

Example 123 General Procedure (H1)[(2-{3-[2-(2,3-Dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazole-4-carbonyl)amino]aceticacid methyl ester

¹H NMR (DMSO): δ 11.26 (s, 1H), 9.20 (s 1H), 8.26 (t, 1H), 8.09 (dd,1H), 7.77 (s, 1H), 7.10 (t, 1H), 6.95 (dd, 1H), 6.79 (t, 1H), 6.72-6.67(m, 2H), 4.01 (d, 2H), 3.84 (s, 3H), 3.66 (s, 3H), 3.65 (s, 3H).

Example 124 General Procedure (H)(5-{3-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}-[1,3,4]thiadiazol-2-yl)aceticacid ethyl ester

¹H NMR (DMSO): δ 11.35 (s, 1H), 9.31 (s 1H), 8.03 (t, 1H), 8.04 (dd,1H), 7.31 (dd, 1H), 7.10-7.02 (m, 2H), 6.75 (t, 1H), 6.55 (dd, 1H),4.19-4.14 (m, 4H), 3.80 (s., 3H), 1.23 (t, 3H).

HPLC-MS (Method B): m/z=465 (M+1); R_(t)=4.14 min.

Example 125 General Procedure (H1)[(2-{3-[2-(2,3-Dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazole-4-carbonyl)amino]aceticacid

,CH₃

¹H NMR (DMSO): δ 12.67 (br, 1H), 11.36 (s, 1H), 9.24 (s 1H), 8.08 (dd,1H), 7.78 (s, 1H), 7.10 (t, 1H), 6.95 (dd, 1H), 6.79 (t, 1H), 6.72-6.67(m, 2H), 3.93 (d, 2H), 3.84 (s, 3H), 3.67 (s, 3H).

HPLC-MS (Method B): m/z=491 (M+1); R_(t)=3.58 min.

Example 126 General Procedure (H)(5-{3-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}-[1,3,4]thiadiazol-2-yl)aceticacid

¹H NMR (DMSO): δ 12.96 (br, 1H), 11.33 (br, 1H), 9.31 (s 1H), 8.04 (dd,1H), 7.33 (dd, 1H), δ 7.11-7.01 (m, 2H), 6.75 (t, 1H), 6.55 (dd, 1H),4.10 (s, 2H), 3.80 (s, 3H).

HPLC-MS (Method B): m/z=337 (M+1); R_(t)=3.47 min.

Example 127 General Procedure (H)5-{3-[2-(2,3-Dimethoxyphenoxy)-5-fluorophenyl]ureido}-[1,3,4]thiadiazole-2-carboxylicacid ethyl ester

¹H NMR (DMSO): δ 11.91 (s, 1H), 9.26 (s 1H), 8.05 (dd, 1H), 7.10 (t,1H), 6.95 (dd, 1H), 6.83 (t, 1H), 6.75-6.67 (m, 2H), 4.40 (q, 2H), 3.84(s, 3H), 3.66 (s, 3H), 1.35 (t, 3H).

HPLC-MS (Method B): m/z=463 (M+1); R_(t)=4.34 min.

Example 128 General Procedure (H)(5-{3-[2-(2,3-Dimethoxyphenoxy)-5-fluorophenyl]ureido}-[1,3,4]thiadiazol-2-yl)aceticacid ethyl ester

HPLC-MS (Method B): m/z=477 (M+1); R_(t)=4.10 min.

Example 129 General Procedure (H1)3-[2-(2-{3-[2-(2,3-Dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazol-4-yl)acetylamino]propionicacid methyl ester

¹H NMR (DMSO): δ 11.11 (s, 1H), 9.07 (br 1H), 8.08 (dd, 1H), 7.98 (t,1H), 7.08 (d, 1H), 6.94 (dd, 1H), 6.81 (s, 1H), 6.77 (dd, 1H), 6.70 (dd,1H), 6.65 (dd, 1H), 3.84 (s, 3H), 3.66 (s, 3H), 3.58 (s, 3H), 3.39 (s,2H), 3.27 (q, 2H), 2.46 (t, 2H).

HPLC-MS (Method B): m/z=533 (M+1); R_(t)=3.71 min.

Example 130 General Procedure (H1)2-(2-{3-[2-(2,3-Dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazol-4-yl)-N-(2-morpholin-4-ylethyl)acetamide

¹H NMR (DMSO): Selected data δ 11.11 (br, 1H), 9.08 (br 1H), 8.07 (dd,1H), 7.09 (t, 1H), 6.94 (dd, 1H), 6.86 (s, 1H), 6.77 (t, 1H), 6.70 (dd,1H), 6.66 (dd, 1H), 3.84 (s, 3H), 3.66 (s, 3H), 3.43 (s, 2H), 3.03-2.99(m, 4H), 1.74-1.71 (m, 4H).

HPLC-MS (Method B): m/z=560 (M+1); R_(t)=2.75 min.

Example 131 General Procedure (H1)[(2-{3-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazole-4-carbonyl)amino]aceticacid methyl ester

¹H NMR (DMSO): δ 11.27 (s, 1H), 9.36 (s 1H), 8.32 (t, 1H), 8.07 (dd,1H), 7.79 (s, 1H), 7.33 (dd, 1H), 7.11-7.02 (m, 2H), 6.75 (t, 1H), 6.55(dd, 1H); 4.03 (d, 2H), 3.80 (s, 3H), 3.66 (s, 3H).

HPLC-MS (Method B): m/z=493 (M+1); R_(t)=3.91 min.

Example 132 General Procedure (H1)3-[2-(2-{3-[2-(2,3-Dimethoxyphenoxy)-5-fluorophenyl]ureido}thiazol-4-yl)acetylamino]propionicacid

¹H NMR (DMSO): δ 12.21 (br, 1H), 11.09 (br, 1H), 9.06 (br 1H), 8.07 (dd,1H), 7.98 (t, 1H), 7.09 (t, 1H), 6.94 (dd, 1H), 6.81 (s, 1H), 6.76 (t,1H), 6.71 (t, 1H), 6.66 (dd, 1H), 3.84 (s, 3H), 3.66 (s, 3H), 3.39 (s,2H), 3.24 (q, 2H), 2.38 (t, 2H).

Example 133 General Procedure (H1)[(2-{3-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazole-4-carbonyl)amino]aceticacid

¹H NMR (DMSO): δ 12.74 (br, 1H), 11.23 (s, 1H), 9.31 (s 1H), 8.17 (t,1H), 8.07 (dd, 1H), 7.78 (s, 1H), 7.33 (dd, 1H), 7.11-7.01 (m, 2H), 6.75(t, 1H), 6.54 (dd, 1H), 3.92 (d, 2H), 3.80 (s, 3H).

Example 134 General Procedure (H1) (R)3-[(2-{3-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazole-4-carbonyl)amino]-2-hydroxy-propionicacid

¹H NMR (DMSO): δ 12.62 (br, 1H), 11.32 (s, 1H), 9.23 (s 1H), 8.06 (dd,1H), 7.79-7.76 (m, 2H), 7.33 (dd, 1H), 7.11-7.02 (m, 2H), 7.06 (dd, 1H),6.75 (t, 1H), 6.54 (dd, 1H), 5.62 (br, 1H), 4.16 (t, 1H), 3.80 (s, 3H),3.64-3.52 (m, 1H), 3.49-3.40 (m, 1H).

HPLC-MS (Method B): m/z=509 (M+1); R_(t)=3.49 min.

Example 135 General Procedure (H1)2-[(2-{3-[5-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]ureido}thiazole-4-carbonyl)amino]-3-hydroxy-propionicacid

¹H NMR (DMSO): δ 12.88 (br, 1H), 11.42 (s, 1H), 9.17 (s 1H), 8.06 (dd,1H), 7.92 (d, 1H), 7.80 (s, 1H), 7.32 (dd, 1H), 7.11-7.01 (m, 2H), 6.75(t, 1H), 6.54 (dd, 1H), 5.10 (br, 1H), 4.46-4.43 (m, 1H), 3.89 (m, 4H).

Example 1361-(2-Cyclopentanecarbonyl-4-methylphenyl)-3-thiazol-2-yl-urea

2-Cyclopentanecarbonyl-4-methylaniline (10.2 g) is prepared fromp-toluidine (10.7 g, 0.1 mol) and cyclopentanecarbonitrile (9.5 g, 0.1mol) following the general procedure I.1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-thiazol-2-yl-urea (132 mg)is prepared from 2-cyclopentanecarbonyl-4-methylaniline (102 mg, 0.5mmol) and 2-aminothiazole (0.060 g, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 330 (M+1)⁺

¹H NMR (400 MHz, CDCl₃): δ 1.69 (m, 2H), 1.91 (m, 2H), 2.37 (s, 3H),3.76 (m, 1H), 6.89 (d, 1H), 7.35 (d, 1H), 7.71 (s, 2H), 8.42 (d, 1H),11.57 (br, 1H) ppm.

Example 137 1-(2-Isobutyryl-4-methylphenyl)-3-thiazol-2-yl-urea

2-Isopropylcarbonyl-4-methylaniline (7.0 g) is prepared from p-toluidine(10.7 g, 0.1 mol) and isobutyronitrile (6.9 g, 0.1 mol) following thegeneral procedure I. 1-(2-Isobutyryl-4-methylphenyl)-3-thiazol-2-yl-urea(113 mg) is prepared from 2-isopropylcarbonyl-4-methylaniline (88 mg,0.5 mmol) and 2-aminothiazole (0.060 g, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 304 (M+1)⁺

¹H NMR (400 MHz, CDCl₃): δ 1.97 (d, 6H), 2.37 (s, 3H), 3.72 (m, 1H),6.90 (d, 1H), 7.36 (d, 1H), 7.69 (s, 2H), 8.44 (s, 1H), 11.51 (br, 1H),11.72 (br, 1H) ppm.

1-[5-Fluoro-2-(3-methylbutyryl)phenyl]-3-thiazol-2-yl-urea

2-[(2-Methyl)-propylcarbonyl]-5-fluoroaniline (6.82 g) is prepared fromm-fluoro aniline (11.1 g, 0.1 mol) and 3-methylbutyronitrile (8.3 g, 0.1mol) following the general procedure I.1-[5-Fluoro-2-(3-methyl-butyryl)-phenyl]-3-thiazol-2-yl-urea (128 mg) isprepared from 2-[(2-methyl)-propylcarbonyl]-5-fluoroaniline (97 mg, 0.5mmol) and 2-aminothiazole (0.060 g, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 322 (M+1)⁺

¹H NMR (400 MHz, CDCl₃): δ 0.99 (d, 6H), 2.23 (m, 1H), 2.83 (d, 2H),6.75 (m, 1H), 6.93 (d, 1H), 7.62 (d, 1H), 7.92 (dd, 1H), 8.43 (dd, 1H),11.60 (br, 1H), 12.04 (br, 1H) ppm.

Example 139 1-[5-Methyl-2-(3-methylbutyryl)phenyl]-3-thiazol-2-yl-urea

2-[2-Methylpropylcarbonyl]-5-methylaniline (6.8 g) is prepared fromm-toluidine (10.2 g, 0.1 mol) and isobutyronitrile (8.3 g, 0.1 mol)following the general procedure I.1-[5-Methyl-2-(3-methylbutyryl)phenyl]-3-thiazol-2-yl-urea (114 mg) isprepared from 2-[2-methylpropylcarbonyl]-5-methylaniline (95 mg, 0.5mmol) and 2-aminothiazole (0.060 g, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 318 (M+1)⁺

¹H NMR (400 MHz, CDCl₃): δ 0.98 (d, 6H), 2.31 (m, 1H), 2.37 (s, 3H),2.44 (d, 2H), 6.91 (m, 1H), 7.27 (m, 1H), 7.51 (d, 1H), 7.68 (dd, 1H),8.45 (d, 1H), 11.58 (br, 1H), 11.60 (br, 1H) ppm.

Example 140[3-Cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)phenyl]acetic acidethyl ester

(4-Amino-3-cyclopentanecarbonylphenyl)acetic acid ethyl ester (2.7 g) isprepared from (4-aminophenyl)acetic acid ethyl ester (18.0 g, 0.1 mol)and cyclopentanecarbonitrile (9.5 g, 0.1 mol) following the generalprocedure I.[3-Cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)phenyl]acetic acidethyl ester (140 mg) is prepared from(4-amino-3-cyclopentane-carbonylphenyl)acetic acid ethyl ester (138 mg,0.5 mmol) and 2-aminothiazole (0.060 g, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 402 (M+1)⁺

¹H NMR (400 MHz, CDCl₃): δ 1.12 (t, 3H), 1.73 (m, 2H), 1.82 (m, 2H),3.27 (m, 1H), 3.62 (s, 2H), 4.15 (q, 2H), 6.89 (d, 1H), 7.44 (dd, 1H),7.62 (d, 1H), 7.86 (s, 1H), 8.51 (s, 1H), 11.62 (br, 1H) ppm.

Example 141[3-Cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)phenyl]acetic acid

[3-Cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)phenyl]acetic acid (168mg) is prepared from[3-cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)phenyl]acetic acidethyl ester (201 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 374 (M+1)⁺

¹H NMR (400 MHz, DMSO-d₆): δ 1.66 (m, 2H), 1.96 (m, 2H), 3.71 (s, 2H),3.92 (m, 1H), 7.05 (d, 1H), 7.38 (d, 1H), 7.56 (dd, 1H), 8.08 (s, 1H),8.55 (s, 1H), 11.26 (br, 1H) ppm.

Example 1422-[3-Cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)phenyl]-N-methylacetamide

2-[3-Cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)-phenyl]-N-methylacetamide(154 mg) is prepared from[3-cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)phenyl]acetic acid (186mg, 0.5 mmol) and 1 M solution of methylamine in THF (0.5 ml, 0.5 mmol)following the general procedure K.

LC-MS (m/z): 387 (M+1)⁺

¹H NMR (400 MHz, CDCl₃/DMSO-d₆): δ 1.51 (m, 2H), 1.73 (m, 2H), 2.58 (s,3H), 3.36 (s, 2H), 3.59 (m, 1H), 6.67 (m, 1H), 7.21 (m, 2H), 7.71 (s,1H), 8.26 (bs, 1H), 10.95 (br, 1H) ppm.

Example 143{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (154 mg) is prepared from(2-amino-5-methylphenyl)(cyclopentyl)methanone (102 mg, 0.5 mmol) andethyl-2-amino-4-thiazolyl acetate (93 mg, 0.5 mmol) following thegeneral procedure D.

LC-MS (m/z): 416 (M+1)⁺

¹H NMR (400 MHz, CDCl₃): δ 1.23 (t, 3H), 1.67 (m, 2H), 1.87 (m, 2H),2.34 (s, 3H), 3.70 (s, 2H), 4.18 (m, 3H), 6.68 (s, 1H), 7.25 (s, 2H),7.32 (d, 1H), 7.67 (s, 1H), 8.45 (s, 1H), 9.75 (br, 1H), 11.51 (br, 1H)ppm.

Example 144{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}aceticacid

{2-[3-(2-Cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazol-4-yl}-aceticacid (198 mg) is prepared from{2-[3-(2-cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (208 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 388 (M+1)⁺

¹H NMR (400 MHz, DMSO-d₆): δ 1.73 (m, 2H), 1.86 (m, 2H), 2.32 (s, 3H),3.55 (s, 2H), 3.86 (m 1H), 6.84 (s, 1H), 7.36 (d, 1H), 7.84 (d, 1H),8.15 (d, 1H), 10.62 (br, 1H), 11.92 (br, 1H), 12.24 (br, 1H) ppm.

Example 145{3-Cyclopentanecarbonyl-4-{3-(4-ethoxycarbonylmethylthiazol-2-yl)-ureido}phenyl}aceticacid ethyl ester

{3-Cyclopentanecarbonyl-4-{3-(4-ethoxycarbonylmethyl-thiazol-2-yl)-ureido}-phenyl}-aceticacid ethyl ester (205 mg) is prepared from(4-amino-3-cyclopentanecarbonyl-phenyl)acetic acid ethyl ester (138 mg,0.5 mmol) and ethyl-2-amino-4-thiazolyl acetate (93 mg, 0.5 mmol)following the general procedure D.

LC-MS (m/z): 488 (M+1)⁺

¹H NMR (400 MHz, CDCl₃): δ 1.24 (t, 6H), 1.67 (m, 2H), 1.88 (m, 2H),2.34 (s, 3H), 3.61 (s, 2H), 3.71 (s, 2H), 3.73 (m, 1H), 4.17 (m, 4H),4.18 (m, 3H), 6.69 (s, 1H), 7.42 (d, 2H), 7.85 (s, 1H), 8.53 (s, 1H),11.64 (br, 1H) ppm.

Example 1461-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea(149 mg) is prepared from 2-cyclopentanecarbonyl-4-methylaniline (102mg, 0.5 mmol) and 5-methanesulfonyl-thiazol-2-yl-amine (106 mg, 0.6mmol) following the general procedure D.

LC-MS (m/z): 408 (M+1)⁺

¹H NMR (400 MHz, CDCl₃): δ 1.65-1.77 (m, 4H), 1.88-1.97 (m, 4H), 2.40(s, 3H), 3.21 (s, 3H), 3.81 (p, 1H), 7.41 (dd, 1H), 7.78 (s, 1H), 8.31(d, 1H), 8.43 (d, 1H), 11.57 (br, 1H), 11.95 (br, 1H) ppm.

Example 1472-[3-(2-Cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazole-4-carboxylicacid ethyl ester

2-[3-(2-Cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazole-4-carboxylicacid ethyl ester (3.6 g) is prepared from2-cyclopentanecarbonyl-4-methyl aniline (2.04 g, 10 mmol) andethyl-2-amino-4-thiazole acetate (1.72 g, 10 mmol) following the generalprocedure D.

LC-MS (m/z): 402 (M+1)⁺

¹H NMR (400 MHz, CDCl₃): δ 1.35 (t, 3H), 1.62-1.78 (m, 4H), 1.83-1.96(m, 4H), 2.37 (s, 3H), 3.74 (p, 1H), 4.33 (q, 2H), 7.36 (d, 1H), 7.72(s, 1H), 7.81 (s, 1H), 8.44 (d, 1H), 9.25 (br, 1H), 11.84 (br, 1H) ppm.

Example 1482-[3-(2-Cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazole-4-carboxylicacid

2-[3-(2-Cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazole-4-carboxylicacid (3.2 g) is prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-4-carboxylicacid ethyl ester (3.6 g, 8.95 mmol) following the general procedure J.

LC-MS (m/z): 374 (M+1)⁺

¹H NMR (400 MHz, DMSO-d₆): δ 1.58 (m, 4H), 1.73 (m, 4H), 2.29 (s, 3H),3.72 (m, 1H), 7.13 (s, 1H), 7.28 (d, 1H), 7.63 (d, 1H), 7.72 (br, 1H),7.94 (s, 1H), 8.22 (br, 1H), 10.92 (br, 1H) ppm.

Example 1492-[3-(2-Cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazole-4-carboxamide

2-[3-(2-Cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazole-4-carboxamide(145 mg) is prepared from2-[3-(2-cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazole-4-carboxylicacid (187 mg, 0.5 mmol) following the general procedure K.

LC-MS (m/z): 373 (M+1)⁺

¹H NMR (400 MHz, DMSO-d₆): δ 1.61 (m, 4H), 1.73 (m, 2H), 1.88 (m, 2H),2.32 (s, 3H), 3.86 (m, 1H), 7.38 (d, 1H), 7.56 (s, 1H), 7.68 (s, 1H),7.84 (s, 1H), 7.93 (s, 1H), 8.14 (d, 1H), 10.73 (br, 1H), 11.86 (br, 1H)ppm.

Example 1502-{2-[3-(2-Cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazole-4-yl}-acetamide

2-{2-[3-(2-Cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazole-4-yl}-acetamide(325 mg) is prepared from2-[3-(2-cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazol-4-yl aceticacid (386 mg, 1.0 mmol) following the general procedure K.

LC-MS (m/z): 387 (M+1)⁺

¹H NMR (400 MHz, DMSO-d₆): δ 1.60 (m, 4H), 1.73 (m, 2H), 1.87 (m, 2H),2.31 (s, 3H), 3.38 (s, 2H), 3.88 (m, 1H), 6.77 (s, 1H), 6.97 (s, 1H),7.38 (d, 2H), 7.83 (s, 1H), 8.15 (d, 1H), 10.63 (br, 1H), 11.81 (br, 1H)ppm.

Example 1512-{2-[3-(2-Cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazol-4-yl}-N-methyl-acetamide

2-{2-[3-(2-Cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazol-4-yl}-N-methyl-acetamide(346 mg) is prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylacetic acid (386 mg, 1.0 mmol) following the general procedure K.

LC-MS (m/z): 401 (M+1)⁺

¹H NMR (400 MHz, DMSO-d₆): δ 1.70 (m, 4H), 1.88 (m, 2H), 1.94 (m, 2H),2.63 (s, 3H), 2.79 (d, 3H), 3.62 (s, 2H), 3.77 (p, 1H), 6.65 (s, 1H),6.77 (br, 1H), 7.35 (dd, 1H), 7.71 (s, 1H), 8.43 (d, 1H), 9.15 (br, 1H),11.70 (br, 1H) ppm.

Example 1524-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazol-4-yl}-acetyl)-1-methyl-piperaziniumchloride

4-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazol-4-yl}-acetyl)-1-methyl-piperazine(337 mg) is prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylaceticacid (386 mg, 1.0 mmol) and N-methylpiperazine following the generalprocedure K.

4-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazol-4-yl}-acetyl)-1-methyl-piperaziniumchloride (392 mg) is prepared from4-(2-{2-[3-(2-cyclopentanecarbonyl-4-methylphenyl)-ureido]-thiazol-4-yl}-acetyl)-1-methyl-piperazine(386 mg, 1.0 mmol) by treatment with anhydrous hydrogen chloride (5 ml,4.0 M solution in dioxane) followed by collection of the solid product.

LC-MS (m/z): 471 (M+1)⁺

¹H NMR (400 MHz, DMSO-d₆): δ 1.60 (m, 4H), 1.72 (m, 2H), 1.87 (m, 2H),2.32 (s, 3H), 2.47 (s, 3H), 2.76 (d, 2H), 2.94 (m, 2H), 3.37 (m, 2H),3.73 (d, 2H), 3.84 (m, 2H), 4.22 (d, 1H), 4.44 (d, 1H), 6.83 (s, 1H),7.36 (d, 1H), 7.82 (s, 1H), 8.11 (d, 1H), 10.63 (br, 1H), 10.82 (br, 1H)ppm.

Example 153 1-[4-Methyl-2-(2-methylpropoxy)phenyl]-3-thiazol-2-yl-urea

3-(2-Methylpropoxy)-4-nitrotoluene (0.78 g) is prepared from2-methylpropanol (0.46 ml, 5.0 mmol) and 3-fluoro-4-nitrotoluene (0.77g, 5.0 mmol) following the general procedure G. This is reduced toafford 4-methyl-2-(2-methylpropoxy)aniline (0.47 g) following generalprocedure C.N-[4-Methyl-2-(2-methylpropoxy)phenyl]-N′-(thiazol-2-yl)urea (210 mg) isprepared from 4-methyl-2-(2-methylpropoxy)aniline (179 mg, 1.0 mmol) and2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

LC-MS (m/z): 306 (M+1)⁺

¹H NMR (400 MHz, CDCl₃): δ 1.01 (d, 6H), 2.16 (m, 1H), 2.32 (s, 3H),3.78 (d, 2H), 6.70 (s, 1H); 6.75 (d, 1H), 6.86 (d, 1H), 7.40 (d, 1H),8.07 (d, 1H), 9.30 (br, 1H), 10.72 (br, 1H) ppm.

Example 154{2-[3-(4-Methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-aceticacid

{2-[3-(4-Methyl-2-[2-methypropoxy]phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (485 mg) is prepared from4-methyl-2-(2-methylpropoxy)aniline (360 mg, 2.0 mmol) and ethyl2-amino-4-thiazolylacetate (372 mg, 2.0 mmol) following the generalprocedure D. Hydrolysis of this ester following general procedure J gave{2-[3-(4-methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-aceticacid (400 mg).

LC-MS (m/z): 464 (M+1)⁺

¹H NMR (400 MHz, DMSO-d₆): δ 1.01 (d, 6H), 2.07 (m, 1H), 2.23 (s, 3H),3.53 (s, 2H), 3.77 (d, 2H), 6.67 (d, 1H), 6.81 (s, 2H), 7.91 (d, 1H),8.01 (br, 1H), 11.45 (br, 1H), 12.35 (br, 1H) ppm.

Example 155{2-[3-(4-Methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-N-methyl-acetamide

{2-[3-(4-Methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-N-methyl-acetamide(150 mg) is prepared from{2-[3-(4-methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-aceticacid (182 mg, 0.5 mmol) following the general procedure K.

LC-MS (m/z): 477 (M+1)⁺

¹H NMR (400 MHz, DMSO-d₆): δ 1.00 (d, 6H), 2.06 (m, 1H), 2.19 (s, 3H),2.48 (s, 3H), 3.40 (s, 2H), 3.68 (d, 2H), 6.54 (s, 1H), 6.59 (d, 2H),7.40 (br, 1H), 7.91 (d, 1H), 8.08 (br, 1H), 11.27 (br, 1H) ppm.

Example 1571-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-methyl-thiazol-2-yl)-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-methyl-thiazol-2-yl)-urea(66 mg, 77%) was prepared from(2-amino-5-methyl-phenyl)-cyclopentyl-methanone (51 mg, 0.25 mmol)following the general procedure D.

LC-MS (m/z): 344 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.60-175 (m, 4H),1.80-194 (m, 4H), 2.32 (s, 3H), 2.36 (s, 3H), 3.73 (p, 1H), 6.44 (s,1H), 7.28 (d, 1H), 7.35 (d, 1H), 7.67 (s, 1H), 8.44 (br, 1H), and 11.66(br, 1H).

Example 1581-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-methoxymethyl-thiazol-2-yl)-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-methoxymethyl-thiazol-2-yl)-urea(64 mg, 69%) was prepared from(2-amino-5-methyl-phenyl)-cyclopentyl-methanone (50 mg, 0.25 mmol) and4-methoxymethyl-thiazol-2-ylamine (54 mg, 0.375 mmol) following thegeneral procedure D to give title compound.

LC-MS (m/z): 373 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.70 (m, 4H), 1.88(m, 4H), 2.36 (s, 3H), 3.41 (s, 2H), 3.72 (m, 1H), 4.44 (s, 3H), 6.78(dd, 1H), 7.32 (d, 1H), 7.70 (s, 1H), 8.42 (d, 1H), 10.52 (br, 1H), and11.64 (br, 1H).

Example 1591-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-formyl-thiazol-2-yl)-urea

To1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-hydroxymethyl-thiazol-2-yl]-urea(1.8 g, 5 mmol) in CH₂Cl₂ (40 mL) at 0° C. was added Et₃N (2.88 mL, 20mmol), dimethyl sulfoxide (10 mL) followed by sulfur trioxide-pyridine(2.38 g, 15.0 mmol). The reaction mixture was stirred for 1 h and thenpoured into water (30 mL). The mixture was extracted with CH₂Cl₂ and theorganic layers was washed with 1.0 N ammonium chloride (2×20 mL), water(2×20 mL), brine (1×20 mL), dried (Na₂SO₄) and concentrated to give asolid. The solid was purified by column chromatography (silica,Hexanes/EtOAc, 20-50%) to obtain1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-formyl-thiazol-2-yl)-urea(1.59 g, 86%) as a white solid.

LC-MS (m/z): 358 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.64 (m, 4H), 1.74(m, 2H), 1.90 (m, 2H), 2.35 (s, 3H), 3.89 (p, 1H), 7.41 (d, 1H), 7.88(s, 1H), 8.17 (d, 1H), 8.24 (s, 1H), 9.76 (s, 1H), 10.75 (s, 1H), and12.20 (br, 1H).

Example 1601-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-hydroxymethyl-thiazol-2-yl)-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-hydroxymethyl-thiazol-2-yl)-urea(2.66 g, 92%) was prepared from acetic acid2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylester (3.2 g, 8.0 mmol) following the general procedure J to give titlecompound.

LC-MS (m/z): 360 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.75 (m, 4H), 1.89(m, 4H), 2.34 (s, 3H), 3.88 (m, 1H), 4.43 (d, 2H), 5.20 (t, 1H), 6.82(s, 1H), 7.39 (d, 1H), 7.85 (s, 1H), 8.18 (d, 1H), 10.66 (br, 1H), and11.72 (br, 1H):

Example 1611-(4-Chloromethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea

1-(4-Chloromethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(2.16 g, 57.1%) was prepared from(2-amino-5-methyl-phenyl)-cyclopentyl-methanone (2.03 g, 10.0 mmol) and4-chloromethyl-thiazol-2-ylamine (1.72 g, 10.0 mmol) following thegeneral procedure D.

LC-MS (m/z): 378 (M+1)⁺, ¹H NMR (400 MHz, CDCl₃): δ 1.68 (m, 4H), 1.88(m, 4H), 2.36 (s, 3H), 3.76 (m, 1H), 4.52 (s, 2H), 6.88 (s, 1H), 7.34(d, 1H), 7.73 (s, 1H), 8.42 (d, 1H), 11.36 (br, 1H), and 11.75 (br, 1H).

Example 1621-(4-Aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea

To a solution of thiourea (7.6 g, 100 mmol) in methanol (150 mL) wasadded 1,3-dicholoroacetone (12.7 g, 100 mmol) and the reaction mixturestirred at rt. for 3-4 hours. The mixture was concentrated in vacuo togive the crude product as hydrochloride salt. This salt was then washedwith Et₂O (3×200 mL) and concentrated in vacuo to afford4-chloromethyl-thiazol-2-ylamine in 95-100% yield.

To a solution of 4-chloromethyl-thiazol-2-ylamine (7.45 g, 50.0 mmol) indioxane:water mixture (8:2) was added sodium azide (4.87 g, 75.0 mmol)and the reaction mixture was refluxed for 2-3 h. The mixture wasconcentrated in vacuo to remove all dioxane and the residue wasdissolved in EtOAc (200 mL). The organic layer was washed with water(2×200 mL), brine (2×200 mL), dried over (Na₂SO₄) and concentrated invacuo to give 4-azidomethyl-thiazol-2-ylamine in 70-90% yield.

(4-Azidomethyl-thiazol-2-ylamine) was subjected to urea formation byfollowing general procedure D to give the desired urea(1-(4-azidomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea)in 65-85% yield.

To a solution of(1-(4-azidomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea)(7.7 g, 20 mmol) in EtOH (100 mL) was added catalytic amount ofpalladium on charcoal (200 mg) and the reaction mixture was hydrogenated(1 atmos) for 3-4 hours to give1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea.This crude product was then purified by flash column chromatography withDCM:EtOAc (80:20 to 50:50) as eluent to give the desired amine (5.7 g,80%).

LC-MS (m/z): 359 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.48 (m, 2H), 1.64(m, 4H), 1.82 (m, 2H), 2.30 (s, 3H), 3.46 (d, 2H), 3.54 (p, 1H), 3.76(t, 2H), 6.84 (s, 1H), 7.07 (s, 1H), 7.76 (d, 1H), 8.32 (d, 1H), 9.64(br, 1H), and 11.18 (br, 1H).

Example 1631-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-dimethylaminomethyl-thiazol-2-yl)-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-dimethylaminomethyl-thiazol-2-yl)-urea(79 mg, 82%) was prepared from2-[3-(2-1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-formyl-thiazol-2-yl)-urea(89 mg, 0.25 mmol) and (30 mg, 0.3 mmol) and dimethylamine (0.1 mL, 2.0M. solution in THF) following the general procedure O to give titlecompound.

LC-MS (m/z): 387 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.62-1.72 (m, 4H),1.78-1.88 (m, 4H), 2.23 (s, 6H), 2.34 (s, 3H), 3.53 (s, 2H), 3.70 (p,1H), 6.64 (s, 1H), 7.30 (d, 1H), 7.64 (s, 1H), 8.32 (d, 1H), 10.25 (br,1H), and 11.35 (br, 1H).

Example 164N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-acetamide

N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-acetamide(88 mg, 88%) was prepared from1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(90 mg, 0.25 mmol) and acetyl chloride (0.02 mL, 0.25 mmol) followingthe general procedure T.

LC-MS (m/z): 401 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.56 (m, 4H), 1.72(m, 2H), 1.78 (m, 2H), 2.22 (s, 3H), 2.82 (s, 3H), 3.18 (t, 1H), 3.64(m, 1H), 4.07 (s, 2H), 6.55 (s, 1H), 7.22 (d, 1H), 7.53 (s, 1H), 8.18(d, 1H), 10.18 (br, 1H), and 11.58 (br, 1H).

Example 1651-{4-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-thiazol-2-yl}-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea

1-{4-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-thiazol-2-yl}-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(425 mg, 87%) was prepared from(2-amino-5-methyl-phenyl)-cyclopentyl-methanone (203 mg, 1.00 mmol) and4-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-thiazol-2-ylamine (310 mg,1.20 mmol) following the general procedure D.

LC-MS (m/z): 488 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 0.10 (s, 9H), 0.85(s, 6H), 1.70-1.78 (m, 4H), 1.82-194 (m, 4H), 2.35 (s, 3H), 2.84 (t,2H), 3.73 (p, 1H), 3.87 (t, 2H), 6.52 (s, 1H), 6.60 (d, 1H), 7.32 (d,1H), 7.72 (s, 1H), 8.48 (br, 1H), 11.68 (br, 1H).

Example 166 Acetic acid2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylester

Acetic acid2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylester (3.66 g, 91%) was prepared from(2-amino-5-methyl-phenyl)-cyclopentyl-methanone (2.03 g, 10.0 mmol) andacetic acid 2-amino-thiazol-4-ylmethyl ester (2.05 g, 12.0 mmol)following the general procedure D.

LC-MS (m/z): 402 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.70 (m, 4H), 1.86(m, 4H), 2.10 (s, 3H), 2.37 (s, 3H), 3.75 (m, 1H), 5.09 (s, 2H), 6.87(s, 1H), 7.35 (d, 1H), 7.71 (s, 1H), 8.45 (d, 1H), 9.20 (br, 1H), and11.75 (br, 1H).

Example 1671-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-1-methyl-3-thiazol-2-yl-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-1-methyl-3-thiazol-2-yl-urea(287 mg, 83%) was prepared fromcyclopentyl-(5-methyl-2-methylamino-phenyl)-methanone (217 mg, 1.00mmol) following the general procedure D.

LC-MS (m/z): 344 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.72 (m, 4H), 1.88(m, 4H), 2.37 (s, 3H), 3.42 (s, 3H), 3.84 (p, 1H), 6.85 (d, 1H), 6.94(d, 1H), 7.17 (d, 1H), 7.43 (d, 1H), 7.46 (s, 1H), and 9.62 (br, 1H).

Example 1681-(5-Chloro-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea

1-(5-Chloro-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(109 mg, 60%) was prepared from(2-amino-5-methyl-phenyl)-cyclopentyl-methanone (102 mg, 0.5 mmol) and5-chloro-thiazol-2-ylamine (0.06 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 364 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.72 (m, 4H), 1.93(m, 4H), 2.38 (s, 3H), 3.80 (m, 1H), 7.37 (d, 1H), 7.64 (s, 1H), 7.74(s, 1H), 8.44 (d, 1H), 11.69 (br, 1H).

Example 1691-(5-Bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea

1-(5-Bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(127 mg, 62%) was prepared from(2-amino-5-methyl-phenyl)-cyclopentyl-methanone (102 mg, 0.5 mmol) and5-bromo-thiazol-2-ylamine (108 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 409 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.72 (m, 4H), 1.93(m, 4H), 2.38 (s, 3H), 3.78 (m, 1H), 7.38 (d, 1H), 7.66 (s, 1H), 7.74(s, 1H), 8.44 (d, 1H), 11.67 (br, 1H).

Example 1701-(5-Bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-5-fluoro-phenyl)-urea

1-(5-Bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-5-fluoro-phenyl)-urea(132 mg, 64%) was prepared from(2-amino-4-fluoro-phenyl)-cyclopentyl-methanone (104 mg, 0.5 mmol) and5-bromo-thiazol-2-ylamine (108 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 413 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.72 (m, 4H), 1.93(m, 4H), 2.38 (s, 3H), 3.74 (m, 1H), 6.81 (m, 1H), 7.61 (s, 1H), 8.01(dd, 1H), 8.42 (dd, 1H), 11.02 (br, 1H), 12.16 (br, 1H).

Example 1712-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-4-methyl-thiazole-5-carboxylicacid ethyl ester

2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-4-methyl-thiazole-5-carboxylicacid ethyl ester (154 mg, 80%) was prepared from(2-amino-5-methyl-phenyl)-cyclopentyl-methanone (102 mg, 0.5 mmol) and2-amino-4-methyl-thiazole-5-carboxylic acid ethyl ester (112 mg, 0.6mmol) following the general procedure D.

LC-MS (m/z): 416 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.33 (t, 3H), 1.66(m, 4H), 1.87 (m, 4H), 2.37 (s, 3H), 2.59 (s, 3H), 3.72 (m, 1H), 4.28(q, 2H), 7.37 (s, 1H), 7.70 (s, 1H), 8.48 (s, 1H), 10.35 (br, 1H), 11.81(br, 1H).

Example 1722-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-4-methyl-thiazole-5-carboxylicacid

2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-4-methyl-thiazole-5-carboxylicacid (198 mg, 95%) was prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-4-methyl-thiazole-5-carboxylicacid ethyl ester (208 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 388 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.66 (m, 4H), 1.74(m, 2H), 1.94 (m, 2H), 2.61 (s, 3H), 2.65 (s, 3H), 3.88 (m, 1H), 7.42(d, 1H), 7.88 (s, 1H), 8.20 (d, 1H), 10.25 (br, 1H), 12.22 (br, 2H).

Example 1731-(2′-Amino-[4,4′]bithiazolyl-2-yl)-3-(2-cyclopentanecarbonyl-4-methylphenyl)-urea

1-(2′-Amino-[4,4′]bithiazolyl-2-yl)-3-(2-cyclopentanecarbonyl-4-methylphenyl)-urea(85 mg, 79%) was prepared from(2-Amino-5-methyl-phenyl)-cyclopentyl-methanone (51 mg, 0.25 mmol)following the general procedure D.

LC-MS (m/z): 428 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.25 (m, 4H), 1.73(m, 4H), 2.37 (s, 3H), 3.77 (p, 1H), 5.24 (br, 2H), 6.99 (s, 1H), 7.02(s, 1H), 7.53 (dd, 1H), 7.58 (s, 1H), 7.72 (s, 1H), 8.42 (br, 1H), and11.78 (br, 1H).

Example 1742-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-N-methoxy-N-methyl-acetamide

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-N-methoxy-N-methyl-acetamide(88 mg, 82. %) was prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thizol-4-yl aceticacid (97 mg, 0.25 mmol) following the general procedure K.

LC-MS (m/z): 431 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.72 (m, 4H), 1.93(m, 4H), 2.35 (s, 3H), 2.80 (s, 2H), 3.70 (s, 3H), 3.85 (s, 3H), 4.21(p, 1H), 6.67 (s, 1H), 6.91 (d, 1H), 7.54 (dd, 1H), 7.70 (d, 1H), 8.40(br, 1H), and 11.52 (br, 1H).

Example 1751-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(2-morpholin-4-yl-2-oxo-ethyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(2-morpholin-4-yl-2-oxo-ethyl)-thiazol-2-yl]-urea(92 mg, 80%) was prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thizol-4-yl aceticacid (97 mg, 0.25 mmol) following the general procedure K.

LC-MS (m/z): 457 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.64 (m, 4H), 1.82(m, 2H), 1.88 (m, 2H), 2.34 (s, 3H), 2.96-3.14 (dd, 2H), 3.49 (t (2H),3.60 (m, 4H), 3.72 (p, 1H), 3.76 (s, 2H), 6.60 (s, 1H), 7.33 (d, 1H),7.67 (s, 1H), 8.42 (d, 1H), 8.70 (br, 1H), and 11.28 (br, 1H).

Example 1762-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-N-(4-methyl-piperazin-1-yl)-acetamide

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-N-(4-methyl-piperazin-1-yl)-acetamide(105 mg, 87%) was prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thizol-4-yl aceticacid (97 mg, 0.25 mmol) following the general procedure K.

LC-MS (m/z): 485 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.66 (m, 4H), 1.82(m, 2H), 1.94 (m, 2H), 2.35 (s, 3H), 3.02 (m, 2H), 3.46 (s, 3H), 3.53 (t(2H), 3.64 (m, 4H), 3.76 (p, 1H), 3.80 (s, 2H), 5.36 (br, 1H), 6.56 (s,1H), 7.34 (d, 1H), 7.69 (s, 1H), 8.46 (d, 1H), 8.82 (br, 1H), and 11.46(br, 1H).

Example 1772-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-N-(2-morpholin-4-yl-ethyl)-acetamide

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-N-(2-morpholin-4-yl-ethyl)-acetamide(108 mg, 86%) was prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thizol-4-yl aceticacid (97 mg, 0.25 mmol) following the general procedure K.

LC-MS (m/z): 500 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.22 (t, 2H), 1.35(t, 4H), 1.70 (m, 2H), 1.86 (m, 2H), 1.94 (m, 2H), 2.32 (s, 3H), 2.88(s, 2H), 2.96 (m, 4H), 3.22 (t, 4H), 3.77 (p, 1H), 5.30 (br, 1H), 6.58(s, 1H), 7.34 (d, 1H), 7.90 (s, 1H), 8.38 (d, 1H), 9.14 (br, 1H), and11.32 (br, 1H).

Example 1782-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-4-carboxylicacid methylamide

2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-4-carboxylicacid methylamide (77 mg, 80%) was prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thizol-4-yl aceticacid (97 mg, 0.25 mmol) following the general procedure K.

LC-MS (m/z): 387 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.74 (m, 4H), 1.82(m, 2H), 1.94 (m, 2H), 2.38 (s, 3H), 3.00 (d, 3H), 3.13 (m, 1H), 3.78(p, 1H), 6.94 (s, 1H), 7.34 (d, 1H), 7.51 (br, 1H), 7.72 (d, 1H), 8.40(d, 1H), and 11.88 (br, 1H).

Example 1791-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(morpholine-4-carbonyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(morpholine-4-carbonyl)-thiazol-2-yl]-urea(92 mg, 80%) was prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thizol-4-yl aceticacid (97 mg, 0.25 mmol) following the general procedure K.

LC-MS (m/z): 443 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.70 (m, 4H), 1.90(m, 4H), 2.36 (s, 3H), 3.12 (m, 2H), 3.76 (m, 4H), 3.82 (m, 1H), 6.69(s, 1H), 7.34 (d, 1H), 7.69 (s, 1H), 8.38 (d, 1H), 9.83 (br, 1H), and11.86 (br, 1H).

Example 180N-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetyl)-methanesulfonamide

N-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetyl)-methanesulfonamide(88 mg, 76%) was prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thizol-4-yl aceticacid (97 mg, 0.25 mmol) following the general procedure K.

LC-MS (m/z): 465 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.72 (m, 4H), 1.92(m, 4H), 2.37 (s, 3H), 3.13 (s, 3H), 3.30 (s, 2H), 3.81 (p, 1H), 4.88(br, 1H), 6.66 (s, 1H), 7.36 (d, 1H), 7.72 (d, 1H), 8.46 (d, 1H), 10.70(br, 1H), and 11.72 (br, 1H).

Example 181N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-4-carbonyl}-methanesulfonamide

N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-4-carbonyl}-methanesulfonamide(103 mg, 91%) was prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thizol-4-yl aceticacid (97 mg, 0.25 mmol) following the general procedure K.

LC-MS (m/z): 451 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.74 (m, 4H), 1.94(m, 4H), 2.32 (s, 3H), 3.11 (s, 3H), 3.32 (p, 1H), 4.66 (br, 1H), 6.62(s, 1H), 7.32 (d, 1H), 7.62 (d, 1H), 8.22 (br, 1H), 8.40 (d, 1H), and11.68 (br, 1H).

Example 1821-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[3-(2-dimethylamino-ethyl)-ureidomethyl]-thiazol-2-yl}-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[3-(2-dimethylamino-ethyl)-ureidomethyl]-thiazol-2-yl}-urea(86 mg, 73%) was prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thizol-4-yl aceticacid (97 mg, 0.25 mmol) following the general procedure M.

LC-MS (m/z): 473 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.40 (t, 2H), 1.72(m, 4H), 1.92 (m, 4H), 2.16 (s, 6H), 2.35 (s, 3H), 2.88 (m, 2H), 3.13(s, 2H), 3.70 (p, 1H), 6.90 (s, 1H), 7.36 (d, 1H), 7.67 (s, 1H), 8.20(d, 1H), 8.44 (br, 1H), 8.92 (br, 1H), 10.26 (br, 1H), and 11.90 (br,1H).

Example 183(3-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-ureido)-aceticacid

(3-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-ureido)-aceticacid (96 mg, 83%) was prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thizol-4-yl aceticacid (97 mg, 0.25 mmol) and glycine methyl ester (48 mg, 0.5 mmol)following the general procedure M followed by hydrolysis using thegeneral procedure J.

LC-MS (m/z): 460 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.70 (m, 4H), 1.90(m, 4H), 2.38 (s, 3H), 3.49 (s, 2H), 3.71 (s, 2H), 3.84 (p, 1H), 6.78(s, 1H), 7.34 (d, 1H), 7.73 (s, 1H), 8.36 (d, 1H), 8.42 (br, 1H), 8.94(br, 1H), 9.86 (br, 1H), 10.26 (br, 1H), and 11.64 (br, 1H).

Example 184{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-carbamicacid 2-dimethylamino-ethyl ester hydrochloride salt

{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-carbamicacid 2-dimethylamino-ethyl ester hydrochloride salt (103 mg, 87%) wasprepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thizol-4-yl aceticacid (97 mg, 0.25 mmol) and 2-N,N-dimethylethanol (0.05 mL, 0.5 mmol)following the general procedure M followed by treatment with HCl inether.

LC-MS (m/z): 474 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.42 (t, 2H), 1.74(m, 4H), 1.92 (m, 4H), 2.28 (s, 6H), 2.39 (s, 3H), 2.96 (m, 2H), 3.24(s, 2H), 3.74 (p, 1H), 6.86 (s, 1H), 7.34 (d, 1H), 7.72 (s, 1H), 8.44(d, 1H), 9.12 (br, 1H), 10.34 (br, 1H), and 11.22 (br, 1H).

Example 185N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-N′,N′-dimethylsulfamide

N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-N′,N′-dimethylsulfamide(104 mg, 89%) was prepared from1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(90 mg, 0.25 mmol) and dimethylsulfamoyl chloride (0.06 mL, 0.5 mmol)following the general procedure T.

LC-MS (m/z): 466 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.72 (m, 4H), 1.88(m, 4H), 2.36 (s, 3H), 2.75 (s, 6H), 3.72 (p, 1H), 4.22 (d, 2H), 6.74(s, 1H), 7.03 (br, 1H), 7.34 (d, 1H), 7.70 (s, 1H), 8.42 (d, 1H), 9.72(br, 1H), and 11.66 (br, 1H).

Example 1863-[{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-(2-methoxycarbonyl-ethyl)-amino]-propionicacid methyl ester

3-[{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-(2-methoxycarbonyl-ethyl)-amino]-propionicacid methyl ester (114 mg, 86%) was prepared by heating1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(90 mg, 0.25 mmol) with methyl acrylate (0.1 mL, 1.1 mmol) and Cs₂CO₃(325 mg, 1.0 mmol) in THF (5 mL) at 60° C. for 2 h followed by columnpurification [silica, DCM:ethyl acetate (80:20 to 20:80)].

LC-MS (m/z): 531 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.68 (m, 4H), 1.84(m, 2H), 2.04 (m, 2H), 2.16 (s, 6H), 2.36 (s, 3H), 2.45 (t, 4H), 3.66(m, 4H), 3.72 (p, 1H), 4.48 (s, 2H), 6.78 (s, 1H), 7.34 (d, 1H), 7.66(s, 1H), 8.44 (d, 1H), 10.54 (br, 1H), and 11.62 (br, 1H).

Example 187({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-methoxycarbonylmethyl-amino)-aceticacid methyl ester

({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-methoxycarbonylmethyl-amino)-aceticacid methyl ester (99 mg, 79%) was prepared by treating1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(90 mg, 0.25 mmol) with methyl bromoacetate (0.04 mL, 0.5 mmol) andpyridine (0.082 mL) in DCM (5 mL) at 60° C. for 2 h followed by columnpurification [silica, DCM:ethyl acetate (80:20 to 20:80)].

LC-MS (m/z): 503 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.53 (m, 4H), 1.76(m, 4H), 2.18 (s, 3H), 2.59-2.74, (m, 6H), 3.50 (s, 6H), 3.62 (m, 1H),6.69 (s, 1H), 7.18 (d, 1H), 7.54 (s, 1H), 8.18 (d, 1H), 10.58 (br, 1H),and 11.28 (br, 1H).

Example 188(Carboxymethyl-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-amino)-aceticacid

(Carboxymethyl-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-amino)-aceticacid (44 mg, 88%) was prepared from({2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-methoxycarbonylmethyl-amino)-aceticacid methyl ester (50 mg, 0.1 mmol) following the general procedure J.

LC-MS (m/z): 474 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 1.53 (m, 4H), 1.76(m, 4H), 2.32 (s, 3H), 2.63 (s, 2H), 2.74 (s, 4H), 3.72 (m, 1H), 6.76(s, 1H), 7.28 (d, 1H), 7.66 (s, 1H), 8.38 (d, 1H), 9.66 (br, 1H), 10.08(br, 2H), and 11.46 (br, 1H).

Example 189N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-2-dimethylamino-acetamide

N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-2-dimethylamino-acetamide(86 mg, 78%) was prepared from1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(90 mg, 0.25 mmol) and N, —N-dimethyl glycine (0.30 mg, 0.30 mmol)following the general procedure K.

LC-MS (m/z): 444 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.70 (m, 4H), 1.92(m, 4H), 2.30 (s, 3H), 2.82 (s, 3H), 2.96 (s, 3H), 3.75 (s, 2H), 3.82(m, 1H), 4.28 (d, 2H), 6.98 (s, 1H), 7.38 (d, 1H), 7.67 (s, 1H), 8.02(d, 1H), 8.44 (br, 1H), 9.22 (br, 1H), and 11.44 (br, 1H).

Example 1901-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-guanidinomethyl-thiazol-2-yl)-urea

To a solution of1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(90 mg, 0.25 mmol) in THF (10 mL) was added pyrrole-1-carboxamidine (54mg, 0.50 mmol) and DIEA (90 μL). The reaction mixture was heated 60° C.for 3 h and concentrated. The crude product was purified by flashchromatography [silica, DCM:ethyl acetate (50:50 to 10:90)] to yield1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-guanidinomethyl-thiazol-2-yl)-urea(88 mg, 88%).

LC-MS (m/z): 401 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.50 (m, 4H), 1.72(m, 4H), 2.23 (s, 3H), 3.08 (q, 1H), 3.62 (p, 1H), 4.26 (br, 2H), 4.32(t, 2H), 6.71 (s, 1H), 7.16 (d, 1H), 7.48 (s, 1H), 7.96 (br, 1H), 8.12(d, 1H), 8.70 (br, 1H), and 10.92 (br, 1H).

Example 1911-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(4-S-methyl-2,5-dioxo-imidazolidin-1-ylmethyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(4-S-methyl-2,5-dioxo-imidazolidin-1-ylmethyl)-thiazol-2-yl]-urea(78 mg, 69%) was prepared from1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(358 mg, 1.0 mmol) and t-Boc-L-alanine (100 mg, 0.80 mmol) following thegeneral procedure U.

LC-MS (m/z): 456 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.43 (d, 3H), 1.64(m, 4H), 1.88 (m, 4H), 2.35 (s, 3H), 3.56 (q, 1H), 3.74 (p, 1H), 4.73(s, 2H), 5.52 (br, 1H), 6.84 (s, 1H), 7.32 (d, 1H), 7.68 (s, 1H), 8.40(d, 1H), 9.84 (br, 1H), and 11.44 (br, 1H).

Example 1921-(4-{[Bis-(3H-imidazol-4-ylmethyl)-amino]-methyl}-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea

1-(4-{[Bis-(3H-imidazol-4-ylmethyl)-amino]-methyl}-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(110 mg, 85%) was prepared from1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(90 mg, 0.25 mmol) and imidazole-2-carboxyaldehyde (48 mg, 0.50 mmol)following the general procedure O.

LC-MS (m/z): 519 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.58 (m, 4H), 1.84(m, 4H), 2.34 (s, 3H), 3.10 (s, 2H), 3.51 (s, 4H), 3.64 (p, 1H), 6.62(s, 1H), 6.84 (s, 1H), 7.08 (s, 1H), 7.11 (d, 1H), 7.66 (d, 1H), 7.70(s, 1H), 7.83 (d, 1H), 8.36 (d, 1H), 8.70 (br, 2H), 9.74 (br, 1H), and11.30 (br, 1H).

Example 1931-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(N′,N′,N″,N″-tetramethyl-guanidinomethyl)-thiazol-2-yl]-urea

1-(4-Aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(90 mg, 0.25 mmol) in DMF were added HBTU (94 mg, 0.25 mmol) and DIEA(90 μL). The reaction mixture was stirred at rt for 2 h. The reactionmixture was poured into water (30 mL) and extracted with ethyl acetate(3×25 mL). The organic layer was washed (water, brine), dried (Na₂SO₄)and concentrated in vacuo. The crude product was purified by flashchromatography [silica, DCM:ethyl acetate (50:50 to 10:90)] to yield1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(N′,N′,N″,N″-tetramethyl-guanidinomethyl)-thiazol-2-yl]-urea(92 mg, 81%).

LC-MS (m/z): 457 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.66 (m, 4H), 1.82(m, 2H), 1.94 (m, 2H), 2.37 (s, 3H), 2.96 (s, 12H), 3.76 (p, 1H), 4.32(s, 2H), 6.80 (s, 1H), 7.38 (d, 1H), 7.70 (s, 1H), 8.38 (d, 1H), 10.54(br, 1H), and 11.58 (br, 1H).

Example 194 2-Amino-ethanesulfonic acid{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-amide

2-Amino-ethanesulfonic acid{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-amide(104 mg, 83%) was prepared from1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(90 mg, 0.25 mmol) and2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethanesulfonyl chloride (70 mg,0.25 mmol) following the general procedure T. This intermediate wasdeprotected by heating with excess of hydrazine (0.2 mL, 1.0 M. in THF).

LC-MS (m/z): 466 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 1.68 (m, 4H), 1.92(m, 4H), 2.38 (s, 3H), 3.22 (t, 2H), 3.68 (m, 2H), 3.76 (p, 1H), 4.08(s, 2H), 4.84 (br, 1H), 5.38 (br, 2H), 6.76 (s, 1H), 7.36 (d, 1H), 7.74(s, 1H), 8.48 (d, 1H), 10.22 (br, 1H), and 11.36 (br, 1H).

Example 195N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-2-methanesulfonylamino-acetamide

N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-2-methanesulfonylamino-acetamide(103 mg, 84%) was prepared from2-amino-N-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-acetamide(104 mg, 0.25 mmol) and methanesulfonyl chloride (0.04 mL, 0.5 mmol)following the general procedure L.

LC-MS (m/z): 494 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.70 (m, 4H), 1.88(m, 4H), 2.36 (s, 3H), 3.28 (t, 2H), 3.38 (s, 3H), 3.74 (p, 1H), 4.16(d, 2H), 6.84 (s, 1H), 6.96 (br, 1H), 7.38 (d, 1H), 7.44 (br, 1H), 7.69(s, 1H), 8.36 (d, 1H), 10.58 (br, 1H), and 11.28 (br, 1H).

Example 196{[({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-carbamoyl)-methyl]-amino}-aceticacid

{[({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-carbamoyl)-methyl]-amino}-aceticacid (44 mg, 88%) was prepared from({2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-methoxycarbonylmethyl-amino)-aceticacid methyl ester (50 mg, 0.1 mmol) following the general procedure J.

LC-MS (m/z): 474 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 1.58 (m, 4H), 1.84(m, 4H), 2.31 (s, 3H), 2.79 (d, 2H), 3.58 (d, 2H) 3.70 (m, 1H), 4.18 (s,2H), 4.96 (br, 1H), 6.82 (s, 1H), 7.03 (br, 1H), 7.30 (d, 1H), 7.72 (s,1H), 8.44 (d, 1H), 9.66 (br, 1H), 10.08 (br, 1H), and 11.46 (br, 1H).

Example 197{[({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-carbamoyl)-methyl]-amino}-aceticacid methyl ester

{[({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-carbamoyl)-methyl]-amino}-aceticacid methyl ester (44 mg, 88%) was prepared by treating2-amino-N-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-acetamide(104 mg, 0.25 mmol) with methyl bromoacetate (0.023 mL, 0.25 mmol) inTHF (5 mL) at 60° C. for 2 h followed by column purification [silica,DCM:ethyl acetate (80:20 to 20:80)].

LC-MS (m/z): 488 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.64 (m, 4H), 1.82(m, 4H), 2.38 (s, 3H), 2.66 (s, 2H), 2.78, (s, 2H), 3.18 (s, 2H), 3.52(s, 3H), 3.72 (m, 1H), 6.76 (s, 1H), 7.06 (br, 1H), 7.28 (d, 1H), 7.66(s, 1H), 8.38 (d, 1H), 8.86 (br, 1H), 9.74 (br, 1H), and 11.46 (br, 1H).

Example 1983-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-sulfamoyl)-propionicacid

3-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-sulfamoyl)-propionicacid (85 mg, 87%) was prepared from3-({2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-sulfamoyl)-propionicacid methyl ester (101 mg, 0.20 mmol) following the general procedure J.

LC-MS (m/z): 495 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 1.74 (m, 4H), 1.88(m, 4H), 2.33 (s, 3H), 3.12 (t, 2H), 3.48 (t, 2H), 3.72 (p, 1H), 3.88(d, 2H), 6.72 (s, 1H), 7.36 (d, 1H), 7.68 (s, 1H), 8.42 (d, 1H), 9.54(br, 1H), 10.88 (br, 1H), 11.12 (br, 1H), and 11.54 (br, 1H).

Example 199N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-2-methanesulfonyl-acetamide

N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-2-methanesulfonyl-acetamide(103 mg, 84%) was prepared from1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(90 mg, 0.25 mmol) and methanesulfonyl acetic acid (55 mg, 0.4 mmol)following the general procedure T.

LC-MS (m/z): 479 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 1.68 (m, 4H), 1.84(m, 4H), 2.35 (s, 3H), 2.78 (s, 2H), 3.12 (s, 3H), 3.86 (m, 1H), 4.08(d, 2H), 6.89 (s, 1H), 7.04 (br, 1H), 7.37 (d, 1H), 7.80 (s, 1H), 8.24(d, 1H), 8.52 (br, 1H), and 11.36 (br, 1H).

Example 2001-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperidine-S-3-carboxylicacid ethyl ester

1-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperidine-S-3-carboxylicacid ethyl ester (107 mg, 86%) was prepared from2-[3-(2-1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-formyl-thiazol-2-yl)-urea(89 mg, 0.25 mmol) and piperidine-S-3-carboxylic acid ethyl ester (40mg, 0.25 mmol) following the general procedure O.

LC-MS (m/z): 499 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.22 (t, 3H),1.63-1.70 (m, 6H), 1.89 (m, 4H), 2.22 (m, 1H), 2.35 (s, 3H), 2.60 (m,2H), 2.84 (m, 2H), 3.00 (d, 2H), 3.55 (m, 2H), 3.72 (p, 1H), 4.10 (q,2H), 6.67 (s, 1H), 7.33 (d, 1H), 7.68 (s, 1H), 8.40 (br, 1H), 10.50 (br,1H), and 11.50 (br, 1H).

Example 2011-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperidine-S-3-carboxylicacid

1-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperidine-S-3-carboxylicacid (104 mg, 81%) was prepared from1-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperidine-S-3-carboxylicacid ethyl ester (135 mg, 0.25 mmol) following the general procedure J.

LC-MS (m/z): 471 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.58-1.64 (m, 4H),1.84-1.96 (m, 6H), 2.16 (m, 1H), 2.28 (s, 3H), 2.80 (m, 1H), 3.05 (m,1H), 3.34-3.49 (m, 2H), 3.66 (d, 1H), 3.93 (m, 1H), 4.34-4.50 (m, 2H),4.70 (m, 1H), 6.83 (s, 1H), 7.36 (d, 1H), 7.60 (s, 1H), 8.25 (d, 1H),9.00 (br, 1H), 10.20 (br, 1H), and 11.36 (br, 1H).

Example 202({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-amino)-(tetrahydro-pyran-4-yl)-aceticacid methyl ester

({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-amino)-(tetrahydro-pyran-4-yl)-aceticacid methyl ester (113 mg, 88%) was prepared from2-[3-(2-1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-formyl-thiazol-2-yl)-urea(89 mg, 0.25 mmol) and amino-(tetrahydro-pyran-4-yl)-acetic acid methylester (44 mg, 0.25 mmol) following the general procedure O.

LC-MS (m/z): 515 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.42 (m, 4H),1.66-1.73 (m, 4H), 1.80-193 (m, 4H), 2.35 (s, 3H), 3.14 (d, 2H), 3.32(t, 2H), 3.64 (t, 2H), 3.72 (p, 1H), 3.78 (d, 2H), 3.92 (s, 3H), 6.24(br, 1H), 6.64 (s, 1H), 7.32 (d, 1H), 7.68 (s, 1H), 8.42 (br, 1H), 9.78(br, 1H), and 11.50 (br, 1H).

Example 203({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-amino)-(tetrahydro-pyran-4-yl)-aceticacid

({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-amino)-(tetrahydro-pyran-4-yl)-aceticacid (87 mg, 87%) was prepared from({2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-amino)-(tetrahydro-pyran-4-yl)-aceticacid methyl ester (128 mg, 0.25 mmol) following the general procedure J.

LC-MS (m/z): 501 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.48 (m, 4H),1.68-1.75 (m, 4H), 1.82-192 (m, 4H), 2.36 (s, 3H), 3.36 (d, 2H), 3.44(t, 2H), 3.68 (t, 2H), 3.74 (p, 1H), 3.82 (d, 2H), 5.24 (br, 1H), 6.76(s, 1H), 7.34 (d, 1H), 7.71 (s, 1H), 8.44 (d, 1H), 9.62 (br, 1H), 10.38(br, 1H), and 11.20 (br, 1H).

Example 2041-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[(2-morpholin-4-yl-ethylamino)-methyl]-thiazol-2-yl}-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[(2-morpholin-4-yl-ethylamino)-methyl]-thiazol-2-yl}-urea(97 mg, 82%) was prepared from2-[3-(2-1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-formyl-thiazol-2-yl)-urea(89 mg, 0.25 mmol) and 2-morpholin-4-yl-ethylamine (35 mg, 0.25 mmol)following the general procedure O.

LC-MS (m/z): 472 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.66 (m, 4H), 1.88(m, 4H), 2.33 (s, 3H), 2.38 (m, 2H), 2.50 (t, 2H), 2.80 (t, 2H),3.59-3.64 (m, 6H), 3.70 p, 1H), 3.85 (m, 2H), 5.88 (br, 1H), 6.58 (s,1H), 7.32 (d, 1H), 7.66 (s, 1H), 8.42 (d, 1H), 10.08 (br, 1H), and 11.28(br, 1H).

Example 2051-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-morpholin-4-ylmethyl-thiazol-2-yl)-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-morpholin-4-ylmethyl-thiazol-2-yl)-urea(83 mg, 78%) was prepared from2-[3-(2-1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-formyl-thiazol-2-yl)-urea(89 mg, 0.25 mmol) and (30 mg, 0.3 mmol) and morpholine (0.25 mL, 0.3mmol) following the general procedure O.

LC-MS (m/z): 429 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.62-1.80 (m, 4H),1.80-1.94 (m, 4H), 2.35 (s, 3H), 2.50 (m, 4H), 3.53 (s, 2H), 3.70 (t,4H), 3.75 (m, 1H), 6.70 (s, 1H), 7.34 (d, 1H), 7.69 (s, 1H), 8.40 (d,1H), 9.75 (br, 1H), and 11.58 (br, 1H).

Example 2061-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(3-oxo-piperazin-1-ylmethyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(3-oxo-piperazin-1-ylmethyl)-thiazol-2-yl]-urea(79 mg, 82%) was prepared from2-[3-(2-1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-formyl-thiazol-2-yl)-urea(89 mg, 0.25 mmol) and piperazine-2-one (30 mg, 0.30 mmol) following thegeneral procedure O.

LC-MS (m/z): 442 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.60-1.74 (m, 4H),1.80-1.94 (m, 4H), 2.35 (s, 3H), 2.67 (t, 2H), 3.30 (s, 2H), 3.38 (m,2H), 3.58 (s, 2H), 3.73 (p, 1H), 6.66 (s, 1H), 7.32 (d, 1H), 7.67 (s,1H), 7.78 (br, 1H), 8.38 (d, 1H), 10.44 (br, 1H), and 11.40 (br, 1H).

Example 207(4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperazin-1-yl)-aceticacid ethyl ester

(4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperazin-1-yl)-aceticacid ethyl ester (79 mg, 82%) was prepared from2-[3-(2-1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-formyl-thiazol-2-yl)-urea(89 mg, 0.25 mmol) and piperazin-1-yl-acetic acid ethyl ester (43 mg,0.25 mmol) following the general procedure O.

LC-MS (m/z): 514 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.28 (t, 3H),1.46-1.62 (m, 4H), 1.66-1.86 (m, 4H), 2.35 (s, 3H), 3.28 (m, 2H), 3.42(s, 2H), 3.40-3-64 (m, 4H), 3.83 (m, 1H), 3.92 (s, 2H), 4.12 (m, 2H),4.48 (s, 2H), 6.84 (s, 1H), 7.29 (d, 1H), 7.67 (s, 1H), 8.28 (d, 1H),11.14 (br, 1H), and 11.62 (br, 1H).

Example 208(4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperazin-1-yl)-aceticacid

(4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperazin-1-yl)-aceticacid (40 mg, 83%) was prepared from(4-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperazin-1-yl)-aceticacid ethyl ester (52 mg, 0.10 mmol) following the general procedure J.

LC-MS (m/z): 486 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.44-1.58 (m, 4H),1.62-1.80 (m, 4H), 2.22 (s, 3H), 2.98 (s, 2H), 3.18 (m, 2H), 3.62 (p,1H), 4.02-4.18 (m, 8H), 7.00 (s, 1H), 7.22 (d, 1H), 7.58 (s, 1H), 8.18(d, 1H), 9.54 (br, 1H), 10.78 (br, 1H), and 11.44 (br, 1H).

Example 2093-(4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperazin-1-yl)-propionicacid ethyl ester

3-(4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperazin-1-yl)-propionicacid ethyl ester (118 mg, 89%) was prepared from2-[3-(2-1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(4-formyl-thiazol-2-yl)-urea(89 mg, 0.25 mmol) and 3-piperazin-1-yl-propionic acid ethyl ester (61mg, 0.30 mmol) following the general procedure O.

LC-MS (m/z): 528 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.24 (t, 3H),1.44-1.64 (m, 4H), 1.64-1.80 (m, 4H), 2.36 (s, 3H), 3.22-3.38 (m, 6H),3.40-3-64 (m, 4H), 3.83 (m, 1H), 3.96 (m, 2H), 4.08 (m, 2H), 4.58 (s,2H), 6.97 (s, 1H), 7.14 (d, 1H), 7.64 (s, 1H), 8.16 (d, 1H), 11.04 (br,1H), and 11.22 (br, 1H).

Example 2103-(4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperazin-1-yl)-propionicacid

3-(4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperazin-1-yl)-propionicacid (38 mg, 76%) was prepared from3-(4-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-piperazin-1-yl)-propionicacid ethyl ester (53 mg, 0.10 mmol) following the general procedure J.

LC-MS (m/z): 500 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.42-1.60 (m, 4H),1.64-1.78 (m, 4H), 2.26 (s, 3H), 3.38-3.44 (m, 6H), 3.48-3.66 (m, 4H),3.77 (m, 1H), 4.02 (m, 2H), 4.64 (s, 2H), 6.88 (s, 1H), 7.30 (d, 1H),7.73 (s, 1H), 8.28 (d, 1H), 9.88 (br, 1H), 10.38 (br, 1H), and 11.34(br, 1H).

Example 211(3-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-ureido)-aceticacid

(3-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-ureido)-aceticacid methyl ester (106 mg, 90%) was prepared from2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thizol-4-yl aceticacid (97 mg, 0.25 mmol) and glycine methyl ester (48 mg, 0.5 mmol)following the general procedure M.

LC-MS (m/z): 460 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.73 (m, 4H), 1.88(m, 4H), 2.36 (s, 3H), 3.46 (s, 2H), 3.66 (s, 2H), 3.78 (p, 1H), 6.74(s, 1H), 7.36 (d, 1H), 7.71 (s, 1H), 8.28 (d, 1H), 8.44 (br, 1H), 8.92(br, 1H), 9.96 (br, 1H), and 11.68 (br, 1H).

Example 2121-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(2,5-dioxo-imidazolidin-1-ylmethyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(2,5-dioxo-imidazolidin-1-ylmethyl)-thiazol-2-yl]-urea(78 mg, 69%) was prepared from1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(358 mg, 1.0 mmol) and t-Boc-glycine (90 mg, 0.80 mmol) following thegeneral procedure U.

LC-MS (m/z): 442 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.66 (m, 4H), 1.90(m, 4H), 2.38 (s, 3H), 3.43 (s, 2H), 3.76 (p, 1H), 4.24 (s, 2H), 5.48(br, 1H), 6.78 (s, 1H), 7.34 (d, 1H), 7.72 (s, 1H), 8.44 (d, 1H), 9.66(br, 1H), and 11.64 (br, 1H).

Example 2134-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-sulfamoyl)-benzoicacid

4-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-sulfamoyl)-benzoicacid (78 mg, 58%) was prepared from1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(90 mg, 0.25 mmol) following the general procedure T.

LC-MS (m/z): 543 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 1.73 (m, 4H), 1.88(m, 4H), 2.33 (s, 3H), 3.68 (m, 2H), 3.74 (p, 1H), 5.88 (br, 1H), 6.82(s, 1H), 7.36 (d, 1H), 7.48 (d, 2H), 7.68 (d, 2H), 7.74 (s, 1H), 8.48(d, 1H), 9.76 (br, 1H), 10.38 (br, 1H), and 11.44 (br, 1H).

Example 2143-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-sulfamoyl)-propionicacid methyl ester

3-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-sulfamoyl)-propionicacid methyl ester (116 mg, 91%) was prepared from1-(4-aminomethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(90 mg, 0.25 mmol) and 3-chlorosulfonyl-propionic acid methyl ester (47mg, 0.25 mmol) following the general procedure T.

LC-MS (m/z): 509 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 1.73 (m, 4H), 1.88(m, 4H), 2.33 (s, 3H), 3.04 (t, 2H), 3.42 (t, 2H), 3.74 (p, 1H), 4.06(d, 2H), 4.26 (s, 3H), 6.58 (s, 1H), 7.32 (d, 1H), 7.72 (s, 1H), 8.48(d, 1H), 9.76 (br, 1H), 10.38 (br, 1H), and 11.52 (br, 1H).

Example 215{2-[3-(2-Cyclopentanecarbonyl-5-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

{2-[3-(2-Cyclopentanecarbonyl-5-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (154 mg, 80%) was prepared from 2-amino-4methyl-phenyl-cyclopentyl-methanone (102 mg, 0.5 mmol) andethyl-2-amino-4-thiazolyl acetate (112 mg, 0.5 mmol) following thegeneral procedure D.

LC-MS (m/z): 416 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.26 (t, 3H), 1.69(m, 4H), 1.88 (m, 4H), 2.41 (s, 3H), 3.70 (s, 2H), 3.72 (m, 1H), 4.18(m, 2H), 6.71 (s, 1H), 6.88 (d, 1H), 7.7.81 (d, 1H), 8.44 (s, 1H), 9.48(br, 1H), 11.82 (br, 1H).

Example 216{2-[3-(2-Cyclopentanecarbonyl-5-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

{2-[3-(2-Cyclopentanecarbonyl-5-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid (175 mg, 90%) was prepared from{2-[3-(2-cyclopentanecarbonyl-5-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (208 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 388 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.74 (m, 4H), 1.87(m, 4H), 2.35 (s, 3H), 3.56 (s 2H), 3.84 (m, 1H), 6.85 (s, 1H), 6.96 (d,1H), 7.95 (d, 1H), 8.17 (s, 1H), 10.96 (br, 1H), 12.22 (br, 1H), 12.40(br, 1H).

Example 217{2-[3-(2-Cyclopentanecarbonyl-5-fluoro-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

{2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (168 mg, 80%) was prepared from 2-amino-4-fluoromethyl-phenyl-cyclopentyl-methanone (103 mg, 0.5 mmol) andethyl-2-amino-4-thiazolyl acetate (112 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 420 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.26 (t, 3H), 1.69(m, 4H), 1.88 (m, 4H), 3.67 (m, 1H), 3.72 (s, 2H), 4.18 (m, 2H), 6.68(d, 1H), 6.75 (m, 1H), 7.93 (t, 1H), 8.44 (d, 1H), 10.20 (br, 1H), 11.90(br, 1H).

Example 218{2-[3-(2-Cyclopentanecarbonyl-5-fluoro-phenyl)-ureido]-thiazol-4-yl}-aceticacid

{2-[3-(2-Cyclopentanecarbonyl-5-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid (180 mg, 92%) was prepared from{2-[3-(2-cyclopentanecarbonyl-5-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (209 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 392 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.61 (m, 4H), 1.74(m, 2H), 1.87 (m, 2H), 3.57 (s 2H), 3.84 (m, 1H), 6.88 (s, 1H), 6.98 (t,1H), 8.21 (m, 2H), 11.23 (br, 1H), 12.20 (br, 1H).

Example 219{2-[3-(4-Bromo-2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

{2-[3-(4-Bromo-2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (192 mg, 80%) was prepared from2-amino-5-bromo-phenyl-cyclopentyl-methanone (134 mg, 0.5 mmol) andethyl-2-amino-4-thiazolyl acetate (112 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 481 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.27 (t, 3H), 1.70(m, 4H), 1.87 (m, 4H), 3.67 (m, 1H), 3.72 (s, 2H), 4.19 (m, 2H), 6.70(s, 1H), 7.59 (dd, 1H), 7.99 (s, 1H), 8.53 (br, 1H), 9.59 (br, 1H),11.56 (br, 1H).

Example 220{2-[3-(4-Bromo-2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

{2-[3-(4-Bromo-2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid (204 mg, 90%) was prepared from{2-[3-(4-bromo-2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (240 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 453 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.72 (m, 4H), 1.82(m, 4H), 3.54 (s 2H), 3.78 (m, 1H), 6.86 (s, 1H), 7.72 (br, 1H), 8.10(br, 1H), 8.22 (s, 1H), 10.65 (br, 1H), 11.70 (br, 1H), 12.40 (br, 1H).

Example 221{4-[3-(5-Chloro-thiazol-2-yl)-ureido]-3-cyclopentanecarbonyl-phenyl}-aceticacid ethyl ester

{4-[3-(5-Chloro-thiazol-2-yl)-ureido]-3-cyclopentanecarbonyl-phenyl}-aceticacid ethyl ester (157 mg, 72%) was prepared from ethyl(4-methylcarboxy)-2-cyclopentanoylaniline (138 mg, 0.5 mmol) and5-chloro-thiazol-2-ylamine (81 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 436 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 0.90 (t, 3H), 1.62(m, 2H), 1.46 (m, 2H), 1.62 (m, 4H), 3.73 (s, 2H), 3.85 (m, 1H), 4.15(q, 2H), 7.42 (s, 1H), 7.48 (d, 1H), 7.98 (s, 1H), 8.20 (d, 1H), 10.79(br, 1H), 12.10 (br 1H).

Example 222{4-[3-(5-Chloro-thiazol-2-yl)-ureido]-3-cyclopentanecarbonyl-phenyl}-aceticacid

{4-[3-(5-Chloro-thiazol-2-yl)-ureido]-3-cyclopentanecarbonyl-phenyl}-aceticacid (180 mg, 88%) was prepared from{4-[3-(5-chloro-thiazol-2-yl)-ureido]-3-cyclopentanecarbonyl-phenyl}-aceticacid ethyl ester (218 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 408 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.73 (m, 4H), 1.89(m, 4H), 3.35 (s, 2H), 3.85 (m, 1H), 7.42 (s, 1H), 7.47 (d, 1H), 7.96(s, 1H), 8.20 (d, 1H), 10.79 (s, 1H), 12.20 (br, 1H),

Example 2232-{4-[3-(5-Chloro-thiazol-2-yl)-ureido]-3-cyclopentanecarbonyl-phenyl}-N-(2-methanesulfonyl-ethyl)-acetamide

2-{4-[3-(5-Chloro-thiazol-2-yl)-ureido]-3-cyclopentanecarbonyl-phenyl}-N-(2-methanesulfonyl-ethyl)-acetamide(180 mg, 70%) was prepared from{4-[3-(5-chloro-thiazol-2-yl)-ureido]-3-cyclopentanecarbonyl-phenyl}-aceticacid (204 mg, 0.5 mmol) and 2-methanesulfonyl-ethylamine (62 mg, 0.5mmol) following the general procedure K.

LC-MS (m/z): 514 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.75 (m, 4H), 1.91(m, 4H), 2.97 (s, 3H), 3.07 (q, 2H), 3.23 (t, 2H), 3.42 (s, 2H), 3.84(m, 1H), 7.42 (s, 1H), 7.44 (d, 1H), 7.94 (s, 1H), 8.18 (d, 1H), 8.35(t, 1H), 10.77 (s, 1H), 12.01 (br, 1H),

Example 224[2-(3-{2-Cyclopentanecarbonyl-4-[(2-methanesulfonyl-ethylcarbamoyl)-methyl]-phenyl}-ureido)-thiazol-4-yl]-aceticacid ethyl ester

[2-(3-{2-Cyclopentanecarbonyl-4-[(2-methanesulfonyl-ethylcarbamoyl)-methyl]-phenyl}-ureido)-thiazol-4-yl]-aceticacid ethyl ester (174 mg, 65%) was prepared from2-(4-amino-3-cyclopentanecarbonyl-phenyl)-N-(2-methanesulfonyl-ethyl)-acetamide(176 mg, 0.5 mmol) and (2-amino-thiazol-4-yl)-acetic acid ethyl ester(112 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 565 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.28 (t, 3H), 1.65(m, 4H), 1.79 (m, 2H), 1.88 (m, 2H), 3.01 (s, 3H), 3.31 (t, 2H), 3.53(s, 2H), 3.68 (s, 2H), 3.83 (m, 1H), 4.20 (m, 3H), 7.42 (s, 1H), 7.44(d, 1H), 7.94 (s, 1H), 8.18 (d, 1H), 8.35 (t, 1H), 10.77 (s, 1H), 12.01(br, 1H),

Example 225 2-(3-{2-Cyclopentanecarbonyl-4-[2-methanesulfonyl-ethylcarbamoyl)-methyl]-phenyl}-ureido)-thiazol-4-yl-acetic acid

2-(3-{2-Cyclopentanecarbonyl-4-[2-methanesulfonyl-ethylcarbamoyl)-methyl]-phenyl}-ureido)-thiazol-4-yl-acetic acid (214 mg,80%) was prepared from2-(3-{2-cyclopentanecarbonyl-4-[2-methanesulfonyl-ethylcarbamoyl)-methyl]-phenyl}-ureido)-thiazol-4-yl-acetic acid ethyl ester(282 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 537 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.65 (m, 4H), 1.79(m, 2H), 1.88 (m, 2H), 2.97 (s, 3H), 3.22 (t, 2H), 3.45 (m, 2H), 3.47(s, 2H), 3.56 (s, 2H), 3.82 (m, 1H), 6.84 (s, 1H), 7.42 (d, 1H), 7.92(s, 1H), 8.18 (d, 1H), 8.33 (t, 1H), 10.70 (s, 1H), 11.84 (br, 1H),

Example 226[3-Cyclopentanecarbonyl-4-(3-[1,3,4]thiadiazol-2-yl-ureido)-phenyl]-aceticacid ethyl ester

3-Cyclopentanecarbonyl-4-(3-[1,3,4]thiadiazol-2-yl-ureido)-phenyl]-aceticacid ethyl ester (147 mg, 73%) was prepared from(4-amino-3-cyclopentanecarbonyl-phenyl)-acetic acid ethyl ester (138 mg,0.5 mmol) and [1,3,4]thiadiazol-2-ylamine (60 mg, 0.6 mmol) followingthe general procedure D.

LC-MS (m/z): 403 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.27 (t, 6H), 1.67(m, 4H), 1.91 (m, 4H), 3.64 (s, 2H), 3.77 (m, 1H), 4.17 (m, 4H), 7.46(d, 1H), 7.89 (s, 2H), 8.47 (s, 1H), 8.77 (s, 1H), 10.40 (br, 1H), 11.89(br, 1H).

Example 2271-[2-Cyclopentanecarbonyl-4-(2-morpholin-4-yl-2-oxo-ethyl)-phenyl]-3-thiazol-2-yl-urea

1-[2-Cyclopentanecarbonyl-4-(2-morpholin-4-yl-2-oxo-ethyl)-phenyl]-3-thiazol-2-yl-urea(151 mg, 68%) was prepared from[3-cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)-phenyl]-acetic acid(186 mg, 0.5 mmol) and morpholine (44 mg, 0.5 mmol) following thegeneral procedure K.

LC-MS (m/z): 443 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃/DMSO-d₆): δ 1.67 (m,4H), 1.88 (m, 4H), 3.51 (t, 4H), 3.69 (t, 4H), 3.74 (m, 3H), 6.91 (d,1H), 7.37 (dd, 1H), 7.64 (d, 1H), 7.84 (s, 1H), 8.52 (br, 2H), 11.32(br, 1H).

Example 2281-{2-Cyclopentanecarbonyl-4-[2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-phenyl}-3-thiazol-2-yl-urea

1-{2-Cyclopentanecarbonyl-4-[2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-phenyl}-3-thiazol-2-yl-urea(137 mg, 60%) was prepared from[3-cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)-phenyl]-acetic acid(186 mg, 0.5 mmol) and N-methyl piperazine (50 mg, 0.5 mmol) followingthe general procedure K.

LC-MS (m/z): 456 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃/DMSO-d₆): δ 1.67 (m,4H), 1.89 (m, 4H), 2.29 (s, 3H), 3.51 (t, 4H), 3.61 (s, 2H), 3.69 (m,5H), 6.92 (d, 1H), 7.38 (d, 1H), 7.58 (s, 1H), 7.84 (s, 1H), 8.53 (d,1H), 11.56 (br, 1H), 11.67 (br, 1H).

Example 229{2-[3-Cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)-phenyl]-acetylamino}-aceticacid

{2-[3-Cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)-phenyl]-acetylamino}-aceticacid tert.butyl ester (158 mg, 65%) was prepared from[3-cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)-phenyl]-acetic acid(186 mg, 0.5 mmol) and glycyne tert.butyl ester (60 mg, 0.5 mmol)following the general procedure K. The ester intermediate (122 mg, 0.25mmol) upon hydrolysis with TFA furnished{2-[3-cyclopentanecarbonyl-4-(3-thiazol-2-yl-ureido)-phenyl]-acetylamino}-aceticacid (86 mg, 80%).

LC-MS (m/z): 431 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃/DMSO-d₆): δ 1.67 (m,4H), 1.94 (m, 4H), 3.69 (dd, 2H), 3.82 (m, 3H), 3.95 (t, 1H), 6.99 (m,1H), 7.32 (dd, 1H), 7.39 (d, 1H), 7.75 (d, 1H), 8.45 (d, 1H), 12.16 (br,1H).

Example 230{2-[3-(2-Cyclopentanecarbonyl-4-methylcarbamoylmethyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

{2-[3-(2-Cyclopentanecarbonyl-4-methylcarbamoylmethyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid (153 mg, 65%) was prepared from2-(4-amino-3-cyclopentane-carbonyl-phenyl)-N-methyl-acetamide (130 mg,0.5 mmol) and (2-amino-thiazol-4-yl)-acetic acid ethyl ester (112 mg,0.6 mmol) following the general procedure D. The ester intermediate (236mg, 0.5 mmol) upon hydrolysis following the general procedure Jfurnished{2-[3-(2-cyclopentanecarbonyl-4-methylcarbamoylmethyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid (167 mg, 75%).

LC-MS (m/z): 445 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.62 (m, 4H), 1.74(m, 2H), 1.90 (m, 2H), 2.57 (d, 3H), 3.43 (s, 2H), 3.56 (s, 2H), 3.81(m, 1H), 6.85 (d, 2H), 7.41 (d, 1H), 7.92 (s, 1H), 7.96 (d, 1H), 8.18(d, 1H), 10.69 (s, 1H), 11.96 (br, 1H).

Example 231{3-Cyclopentanecarbonyl-4-[3-(4-methylcarbamoylmethyl-thiazol-2-yl)-ureido]-phenyl}-aceticacid ethyl ester

{3-Cyclopentanecarbonyl-4-[3-(4-methylcarbamoylmethyl-thiazol-2-yl)-ureido]-phenyl}-aceticacid ethyl ester (153 mg, 65%) was prepared from(4-amino-3-cyclopentane-carbonyl-phenyl)-acetic acid ethyl ester (138mg, 0.5 mmol) and 2-(2-amino-thiazol-4-yl)-N-methyl-acetamide (103 mg,0.6 mmol) following the general procedure D.

LC-MS (m/z): 473 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.26 (t, 3H), 1.70(m, 4H), 1.86 (m, 2H), 1.92 (m, 2H), 2.81 (d, 3H), 3.62 (s, 2H), 3.65(s, 2H), 3.77 (m, 1H), 4.16 (q, 2H), 6.65 (s, 1H), 6.71 (br, 1H), 7.44(dd, 1H), 7.88 (s, 1H), 8.52 (d, 1H), 9.39 (br, 1H), 11.71 (br, 1H).

Example 2322-{3-Cyclopentanecarbonyl-4-[3-(4-methylcarbamoylmethyl-thiazol-2-yl)-ureido]-phenyl}-N-methyl-acetamide

{3-Cyclopentanecarbonyl-4-[3-(4-methylcarbamoylmethyl-thiazol-2-yl)-ureido]-phenyl}-aceticacid (155 mg, 70%) was prepared from{3-cyclopentanecarbonyl-4-[3-(4-methylcarbamoylmethyl-thiazol-2-yl)-ureido]-phenyl}-aceticacid ethyl ester (236 mg, 0.5 mmol) following the general procedure J.The acid (222 mg, 0.5 mmol) was coupled with 1 N methyl amine followingthe general procedure K furnished2-{3-cyclopentanecarbonyl-4-[3-(4-methylcarbamoylmethyl-thiazol-2-yl)-ureido]-phenyl}-N-methyl-acetamide(137 mg, 60%).

LC-MS (m/z): 458 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃/DMSO-d₆): δ 1.69 (m,4H), 1.82 (m, 4H), 2.65 (d, 3H), 3.68 (d, 3H), 3.43 (s, 2H), 3.48 (s,2H), 3.67 (m, 1H), 6.51 (d, 1H), 7.14 (br, 1H), 7.31 (m, 2H), 7.54 (d,1H), 7.75 (dd, 1H), 8.31 (d, 1H), 11.13 (br, 1H).

Example 2331-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(pyridin-2-yloxy)-ethyl]-thiazol-2-yl]-urea

To a solution of{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid (0.38 g, 1.0 mmol) in THF (5 mL) at 0° C. was added 1.0 M solutionof BH₃-THF (3.0 mL, 3.0 mmol) dropwise. After stirring at 0° C. for 1 h,the excess BH₃-THF complex was quenched with MeOH. The solution wasconcentrated under vacuum and purified on silica gel with 1:1EtOAc/hexanes to obtain the alcohol as a white powder in 80% yield.

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(pyridin-2-yloxy)-ethyl]-thiazol-2-yl}-urea(30 mg, 50%) was prepared from1-[2-(cyclopentanecarbonyl-4-methyl-phenyl]-3-[4-(2-hydroxy-ethyl)-thiazol-2-yl]-urea(0.05 g, 0.134 mmol), 2-hydroxypyridine (0.013 g, 0.143 mmol) followingthe general procedure P.

LC/MS (m/z): 451 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) δ 1.67-1.72 (m, 4H),1.89-1.85 (m, 4H), 2.36 (s, 3H), 3.13 (t, 2H), 3.64-3.80 (m, 1H), 4.60(t, 2H), 6.60 (s, 1H), 6.72 (d, 1H), 6.86 (m, 1H), 7.34 (d, 1H), 7.56(m, 1H), 7.70 (s, 1H), 8.15 (d, 1H), 8.45 (br, 1H), 11.85 (br, 1H).

Example 2341-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(pyridin-4-yloxy)-ethyl]-thiazol-2-yl}-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(pyridin-4-yloxy)-ethyl]-thiazol-2-yl}-urea(50 mg, 42%) was prepared from1-[2-(cyclopentanecarbonyl-4-methyl-phenyl]-3-[4-(2-hydroxy-ethyl)-thiazol-2-yl]-urea(0.10 g, 0.27 mmol) and 4-hydroxypyridine (0.05 g, 0.54 mmol) followingthe general procedure P.

LC/MS (m/z): 451 (M+1)⁺, ¹H NMR (400 MHz, CDCl₃) δ 1.62-1.73 (m, 4H),1.80-1985 (m, 4H), 2.37 (s, 3H), 2.85 (t, 2H), 3.87 (t, 2H), 3.75 (br,1H), 6.52 (s, 1H), 7.46 (d, 2H) 7.48 (d, 2H), 7.52 (d, 1H), 7.70 (s,1H), 8.44 (d, 1H),

Example 2355-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)nicotinicacid methyl ester

5-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)nicotinicacid methyl ester (30 mg, 44%) was prepared from1-[2-(cyclopentanecarbonyl-4-methyl-phenyl]-3-[4-(2-hydroxy-ethyl)-thiazol-2-yl]-urea(0.05 g, 0.134 mmol) and 5-hydroxynicotinic acid methyl ester (0.04 g,0.27 mmol) following the general procedure P.

LC/MS (m/z): 509 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD) δ 1.65-1.74 (br, 4H),1.83-1.89 (br, 4H), 2.35 (s, 3H), 3.15 (t, 2H), 3.74 (br, 1H), 3.92 (s,3H), 4.42 (t, 2H), 6.75 (s, 1H), 7.72 (s, 1H), 7.85 (d, 1H), 8.27 (s,1H), 8.42 (d, 1H), 8.57 (s, 1H), 8.67 (s, 1H),

Example 2365-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)nicotinicacid

5-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)nicotinicacid (23 mg, 95%) was prepared from5-(2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)nicotinicacid methyl ester (0.025 g, 0.05 mmol) and 2.5M LiOH (20 ul) followingthe general procedure J.

LC/MS (m/z): 495 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD) δ 1.65-1.75 (br, 4H),1.83-1.90 (br, 4H), 2.31 (s, 3H), 3.05 (t, 2H), 3.72-3.80 (m, 1H), 4.42(t, 2H), 6.85 (s, 1H), 7.57 (s, 1H), 7.74 (d, 1H), 8.30 (s, 1H), 8.48(d, 1H), 8.52 (s, 1H), 8.65 (s, 1H), 11.43 (br, 1H).

Example 2374-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)benzoicacid methyl ester

4-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)benzoicacid methyl ester (50 mg, 37%) was prepared from1-[2-(cyclopentanecarbonyl-4-methyl-phenyl]-3-[4-(2-hydroxy-ethyl)-thiazol-2-yl]-urea(0.10 g, 0.27 mmol) and 4-hydroxybenzoic acid methyl ester (0.08 g, 0.54mmol) following the general procedure P.

LC/MS (m/z): 508 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) δ 1.64-1.78 (m, 4H),1.82-1.90 (m, 4H), 2.32 (s, 3H), 3.04 (t, 2H), 3.60-3.85 (m, 1H), 3.92(s, 3H), 4.32 (t, 2H), 6.81 (s, 1H), 6.98 (d, 2H), 7.33 (d, 1H), 7.80(s, 1H), 7.86 (d, 2H), 8.15 (br, 1H), 10.70 (br, 1H), 11.88 (br, 1H).

Example 2384-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)benzoicacid

4-(2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)benzoicacid (19 mg, 96%) was prepared from4-(2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)benzoicacid methyl ester (0.020 g, 0.04 mmol) and 2.5M LiOH (20 uL) followingthe general procedure J.

LC/MS (m/z): 494 (M+1)⁺; ¹H NMR (400 MHz, DMSO) d 1.65-1.78 (m, 4H),1.80-1.92 (m, 4H), 2.32 (s, 3H), 3.04 (t, 2H), 3.60-3.85 (m, 1H), 4.34(t, 2H), 6.82 (s, 1H), 7.01 (d, 2H), 7.36 (d, 2H), 7.81 (s, 1H), 7.86(d, 2H), 8.13 (br, 1H), 8.88 (s, 1H), 10.66 (br, 1H).

Example 239[4-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)-phenyl]aceticacid methyl ester

[4-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)-phenyl]aceticacid methyl ester (56 mg, 40%) was prepared from1-[2-(cyclopentanecarbonyl-4-methyl-phenyl]-3-[4-(2-hydroxy-ethyl)-thiazol-2-yl]-urea(0.10 g, 0.27 mmol) and 4-hydroxyphenylacetic acid methyl ester (0.09 g,0.54 mmol) following the general procedure P.

LC/MS (M/Z): 522 (M+1)⁺.

Example 240[4-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)-phenyl]aceticacid

[4-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)-phenyl]aceticacid (25 mg, 86%) was prepared from[4-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)-phenyl]aceticacid methyl ester (0.03 g, 0.06 mmol) and 2.5M LiOH (20 uL) followingthe general procedure J.

LC/MS (m/z): 508 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) δ 1.65-1.76 (m, 4H),1.83-1.95 (m, 4H), 2.36 (s, 3H), 3.10 (t, 2H), 3.70-3.82 (m, 1H), 4.24(t, 2H), 4.96-5.02 (m, 2H), 6.50 (s, 1H), 6.88 (d, 2H), 7.20 (d, 2H),7.30 (d, 1H), 7.68 (s, 1H), 8.45 (br, 1H), 11.45 (br, 1H).

Example 2411-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(2-morpholin-4-yl-ethyl)-thiazol-2-yl]-urea

To1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(2-hydroxy-ethyl)-thiazol-2-yl]-urea(2.68 mmol) in CH₂Cl₂ (20 mL) at 0° C. was added Et₃N (1.64 mL, 11.70mmol), dimethyl sulfoxide (10 mL) followed by sulfur trioxide-pyridine(1.46 g, 9.21 mmol). The reaction mixture was stirred for 1 h and thenpoured into water (30 mL), The mixture was extracted with CH₂Cl₂ and theorganic layers was washed with 1.0 N ammonium chloride (2×20 mL), water(2×20 mL), brine (1×20 mL), dried (Na₂SO₄) and concentrated to give asolid. The solid was purified by column chromatography (silica,Hexanes/EtOAc, 20-50%) to obtain the aldehyde as a white solid in 50%yield.

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(2-morpholin-4-yl-ethyl)-thiazol-2-yl]-urea(15 mg, 31%) was prepared from1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(2-oxo-ethyl)-thiazol-2-yl]-urea(0.04 g, 0.11 mmol) and morpholine (0.009 g, 0.11 mmol) following thegeneral procedure O.

LC/MS (m/z): 443 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) δ 1.68-1.72 (m, 4H),1.88-1.91 (m, 4H), 2.36 (s, 3H), 2.53 (br, 4H), 2.72 (t, 2H), 2.85 (t,2H), 3.72-3.74 (m, 5H), 6.52 (s, 1H), 7.35 (d, 1H), 7.70 (s, 1H), 8.45(br, 1H), 11.62 (br, 1H).

Example 2421-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-thiazol-2-yl}-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-thiazol-2-yl}-urea(23 mg, 44%) was prepared from (0.04 g, 0.11 mmol) and 4-ethylaminomorpholine (0.014 g, 0.11 mmol) following the general procedure O.

LC/MS (m/z): 486 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) δ 1.69-1.73 (m, 4H),1.88-1.92 (m, 4H), 2.35 (s, 3H), 2.50 (t, 2H), 2.53 (br, 4H), 2.72 (t,2H), 2.80 (t, 2H), 2.85 (t, 2H), 3.72-3.74 (m, 5H), 6.53 (s, 1H), 7.35(d, 1H), 7.70 (s, 1H), 8.45 (br, 1H), 11.60 (br, 1H).

Example 2431-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethyl)-piperidin-3-carboxylicacid ethyl ester

1-(2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethyl)-piperidin-3-carboxylicacid ethyl ester (28 mg, 50%) was prepared from (0.04 g, 0.11 mmol) and(s)-(+)-nipecotic acid (0.017 g, 0.11 mmol) following the generalprocedure O.

LC/MS (m/z): 528 (M+1)⁺.

Example 2441-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethyl)-piperidin-3-carboxylicacid

1-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethyl)-piperidin-3-carboxylicacid (18 mg, 95%) was prepared from1-(2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethyl)-piperidin-3-carboxylicacid ethyl ester (0.02 g, 0.04 mmol) and 2.5M LiOH (20 uL) following thegeneral procedure J.

LC/MS (m/z): 513 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) δ 1.60-1.69 (m, 4H),1.80-1.98 (m, 4H), 2.34 (s, 3H), 2.90-3.05 (m, 5H), 3.10-3.20 (m, 4H),3.65-3.75 (m, 1H), 6.49 (s, 1H), 7.34 (d, 1H), 7.63 (s, 1H), 8.25 (d,1H), 11.40 (br, 1H).

Example 2451-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(2-piperazin-1-yl-ethyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(2-piperazin-1-yl-ethyl)-thiazol-2-yl]-urea(35 mg, 70%) was prepared from methanesulfonic acid2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethylester (0.06 g, 0.13 mmol) and piperazine (0.50 g, 5.82 mmol) followingthe general procedure Z. LC/MS (m/z): 442 (M+1)⁺; ¹H NMR (400 MHz,CDCl₃) δ 1.66-1.72 (m, 4H), 1.86-1.90 (m, 4H), 2.36 (s, 3H), 2.45-2.60(br, 4H), 2.71 (t, 2H), 2.84 (t, 2H), 2.89-2.98 (m, 4H), 3.70-3.80 (m,1H), 6.47 (s, 1H), 7.34 (d, 1H), 7.69 (s, 1H), 8.45 (br, 1H), 11.45 (br,1H).

Example 2461-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(4-methanesulfonyl-piperazin-1-yl-ethyl]-thiazol-2-yl}-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(4-methanesulfonyl-piperazin-1-yl-ethyl]-thiazol-2-yl}-urea(14 mg, 40%) was prepared from1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(2-piperazin-1-yl-ethyl)-thiazol-2-yl]-urea(0.03 g, 0.07 mmol) and sulfonyl chloride (0.008 g, 0.068 mmol)following the general procedure T.

LC/MS (m/z): 520 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) δ 1.65-1.75 (m, 4H),1.85-1.95 (m, 4H), 2.37 (s, 3H), 2.60-2.64 (br, 4H), 2.76-2.95 (m, 4H),2.78 (s, 3H), 3.25 (br, 4H), 3.70-3.80 (m, 1H), 6.50 (s, 1H), 7.35 (d,1H), 7.70 (s, 1H), 8.45 (br, 1H), 11.65 (br, 1H).

Example 2471-[4-(2-Amino-ethyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea

1-[4-(2-Amino-ethyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(0.15 g, 94%) was prepared from1-[4-(2-azido-ethyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(0.17 g, 0.43 mmol) following the general procedure T.

LC/MS (m/z): 373 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) δ 1.68-1.74 (m, 4H),1.88-1.93 (m, 4H), 2.36 (s, 3H), 2.84 (t, 2H), 3.28 (t, 2H), 3.72-3.80(m, 1H), 4.5 (br, 2H), 6.47 (s, 1H), 7.34 (d, 1H), 7.69 (s, 1H), 8.55(d, 1H), 11.34 (br, 1H).

Example 2483-(2-{-2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethylamino)-propionic acid

1-[4-(amino-ethyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(0.03 g, 0.08 mmol) and succinic anhydride (0.02 g, 0.16 mmol) in 10 mLDCM were refluxed for 2 h. Reaction was concentrated and purified onsilica gel using 5% MeOH/EtOAc to yield the pure product (20 mg, 53%).

LC/MS (m/z): 473 (M+1)⁺; ¹H NMR (400 MHz, DMSO) δ 1.60-1.75 (m, 4H),1.85-1.92 (m, 4H), 2.38 (s, 3H), 2.67 (t, 2H), 3.28-3.32 (m, 4H),3.80-3.92 (br, 1H), 4.02 (t, 2H), 6.70 (s, 1H), 7.38 (d, 1H), 7.83 (s,1H), 8.15 (d, 1H), 10.65 (br, 1H).

Example 249(2-{-2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethylamino)-acetic acid methyl ester

To1-[4-(amino-ethyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(0.03 g, 0.08 mmol) in 10 mL DCM was added methyl bromoacetate (0.01 g,0.08 mmol) followed by Et₃N (0.008 g, 0.08 mmol). After stirring at roomtemperature overnight, reaction was concentrated and purified by flashchromatography on silica gel with 5% MeOH/EtOAc to obtain the product in50% yield.

LC/MS (m/z): 445 (M+1)⁺

Example 250(2-{-2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethylamino)-acetic acid

(2-{-2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethylamino)-acetic acid (18 mg, 95%) was prepared from(2-{-2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethylamino)-acetic acid ethyl ester (0.02 g, 0.05 mmol) and 2.5M LiOH (20 uL)following the general procedure J.

LC/MS (m/z): 431 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) δ 1.63-1.74 (m, 4H),1.86-1.92 (m, 4H), 2.36 (s, 3H), 2.81 (t, 2H), 3.07 (t, 2H), 3.59 (s,2H), 3.69-3.76 (m, 1H), 6.54 (s, 1H), 7.33 (d, 1H), 7.70 (s, 1H), 8.46(br, 1H), 11.60 (br, 1H).

Example 251N-(2-{-2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethyl)-acetamide

To1-[4-(amino-ethyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(0.05 g, 0.13 mmol) in 10 mL DCM at 0° C. was added acetyl chloride(0.02 g, 0.27 mmol) followed by pyridine (0.02 g, 0.21 mmol). Afterstirring for 3 h, reaction was concentrated and purified by flashchromatography on silica gel with 50% EtOAc/hexane to obtain the productin 64% yield.

LC/MS (m/z): 415 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) δ 1.65-1.75 (m, 4H),1.84-1.90 (m, 4H), 1.97 (s, 3H), 2.37 (s, 3H), 2.84 (t, 2H), 3.58 (t,2H), 3.70-3.80 (m, 1H), 6.54 (s, 1H), 7.34 (d, 1H), 7.70 (s, 1H), 8.45(br, 1H), 11.65 (br, 1H).

Example 252N-(2-{-2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethyl)-methanesulfonamide

To1-[4-(amino-ethyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(0.05 g, 0.13 mmol) in 10 mL DCM at 0° C. was added methanesulfonylchloride (0.02 g, 0.13 mmol) followed by pyridine (0.02 g, 0.21 mmol).The reaction was stirred at ambient temperature overnight, concentratedand purified by flash chromatography on silica gel with 20-50%EtOAc/hexane to obtain the product as white solid in 75% yield. LC/MS(m/z): 451 (M+1)⁺; ¹H NMR (400 MHz, DMSO) δ 1.62-1.76 (m, 4H), 1.82-1.92(m, 4H), 2.32 (s, 3H), 2.75 (t, 2H), 2.84 (s, 3H), 3.80-3.90 (m, 1H),4.10 (t, 2H), 6.76 (s, 1H), 7.37 (d, 1H), 7.83 (s, 1H), 8.16 (d, 1H),10.64 (br, 1H), 11.80 (br, 1H).

Example 253N-(2-{-2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethyl)-2-dimethylaminoacetamide

N-(2-{-2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethyl)-2-dimethylaminoacetamide (37 mg, 61%) was prepared from1-[4-(amino-ethyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(0.05 g, 0.13 mmol), dimethylamino acetic acid (0.02 g, 0.13 mmol)following the general procedure K.

LC/MS (m/z): 458 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD) δ 1.63-1.70 (m, 4H),1.80-1.95 (m, 4H), 2.36 (s, 3H), 2.70 (s, 6H), 2.85 (t, 2H), 3.60 (t,2H), 3.62 (s, 2H), 3.86 (br, 1H), 6.65 (s, 1H), 7.38-7.28 (m, 2H),7.65-7.74 (m, 1H), 7.80 (br, 1H), 8.20 (br, 1H),

Example 254N-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethyl)-succinamicacid

1-[4-(amino-methyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(0.10 g, 0.28 mmol) and succinic anhydride (0.08 g, 0.78 mmol) in 10 mLDCM were refluxed for 2 h. Reaction was concentrated and purified onsilica gel using 5% MeOH/EtOAc to yield the desired product (77 mg,60%).

LC/MS (m/z): 459 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD) δ 1.70-1.77 (m, 4H),1.85-1.95 (m, 4H), 2.39 (s, 3H), 2.62-2.72 (m, 4H), 3.71 (s, 2H),3.80-3.90 (m, 1H), 6.08 (s, 1H), 7.40-(d, 1H), 7.75 (s, 1H), 8.70 (d,1H), 11.30 (s, 1H),

Example 2553-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acrylicacid ethyl ester

3-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acrylicacid ethyl ester (70 mg, 58%) was prepared from1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(1-oxo-methyl)-thiazol-2-yl]-urea(0.10 g, 0.28 mmol) and (carbethoxymethylene)-triphenylphosphorane (0.12g, 0.34 mmol) following the general procedure X.

LC/MS (m/z): 428 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) δ 1.29 (t, 3H),1.67-1.75 (m, 4H), 1.80-1.95 (m, 4H), 2.37 (s, 3H), 3.70-3.80 (m, 1H),4.19-4.22 (q, 2H), 6.56 (d, 1H), 7.07 (s, 1H), 7.36 (d, 1H), 7.50 (d,1H), 7.72 (s, 1H), 8.45 (d, 1H),

Example 2563-{2-[3-(2-CYCLOPENTANECARBONYL-4-METHYL-PHENYL)-UREIDO]-THIAZOL-4-YL}-PROPIONICACID ETHYL ESTER

3-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-propionicacid ethyl ester (48 mg, 96%) was prepared by hydrogenation of3-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acrylicacid ethyl ester (0.05 g, 0.12 mmol) with Pd/C.

LC/MS (m/z): 430 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) δ 1.22 (t, 3H),1.64-1.70 (m, 4H), 1.80-1.95 (m, 4H), 2.35 (s, 3H), 2.69 (t, 2H), 2.98(t, 2H), 3.67-3.80 (m, 1H), 4.01-4.15 (q, 2H), 6.50 (s, 1H), 7.32 (d,1H), 7.68 (s, 1H), 8.45 (br, 1H), 11.60 (br, 1H).

Example 2573-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-propionicacid

3-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-propionicacid (15 mg, 88%) was prepared from3-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-propionicacid ethyl ester (0.03 g, 0.04 mmol) and 2.5M LiOH (20 μL) following thegeneral procedure J. LC/MS (m/z): 402 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD) δ1.70-1.80 (m, 4H), 1.82-1.95 (m, 4H), 2.34 (s, 3H), 2.58 (t, 2H), 2.80(t, 2H), 3.82-3.94 (m, 1H), 6.69 (s, 1H), 7.38 (d, 1H), 7.85 (s, 1H),8.19 (br, 1H), 10.65 (br, 1H).

Example 2584-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-but-2-enoicacid ethyl ester

4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-but-2-enoicacid ethyl ester (50 mg, 42%) was prepared from1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(2-oxo-ethyl)-thiazol-2-yl]-urea(0.10 g, 0.27 mmol) and (carbethoxymethylene)-triphenylphosphorane (0.09g, 0.27 mmol) following the general procedure X.

LC/MS (m/z): 442 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) δ 1.28 (t, 3H),1.67-1.73 (m, 4H), 2.37 (s, 3H), 3.56 (d, 1H), 3.70-3.80 (m, 1H),4.15-4.21 (q, 2H), 5.88 (d, 1H), 6.55 (s, 1H), 7.37 (d, 1H), 7.65 (s,1H), 8.43 (br, 1H), 11.65 (br, 1H).

Example 2591-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(1H-imidazol-2-ylsulfanylmethyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(1H-imidazol-2-ylsulfanylmethyl)-thiazol-2-yl]-urea(76 mg, 69%) was prepared from1-(4-Chloromethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(94 mg, 0.25 mmol) following the general procedure Q.

LC-MS (m/z): 442 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.76 (m, 4H), 1.92(m, 4H), 2.32 (s, 3H), 3.88 (p, 1H), 4.43 (s, 2H), 6.94 (s, 1H), 7.11(d, 1H), 7.36 (d, 1H), 7.88 (d, 1H), 7.71 (s, 1H), 8.52 (d, 1H), 10.34(br, 2H), and 11.42 (br, 1H).

Example 2601-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-thiazol-2-yl]-urea(93 mg, 79%) was prepared from1-(4-chloromethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(94 mg, 0.25 mmol) following the general procedure Q.

LC-MS (m/z): 458 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.73 (m, 4H), 1.88(m, 4H), 2.37 (s, 3H), 3.76 (p, 1H), 3.86 (s, 3H), 4.55 (s, 2H), 6.88(s, 1H), 7.34 (d, 1H), 7.70 (s, 1H), 8.40 (d, 1H), 8.52 (br, 1H), and11.78 (br, 1H).

Example 2611-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(9H-purin-6-ylsulfanylmethyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(9H-purin-6-ylsulfanylmethyl)-thiazol-2-yl]-urea(106 mg, 86%) was prepared from1-(4-chloromethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(94 mg, 0.25 mmol) following the general procedure Q.

LC-MS (m/z): 494 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.66 (m, 4H), 1.84(m, 4H), 2.21 (s, 3H), 3.72 (p, 1H), 4.29 (s, 2H), 4.63 (br, 1H), 6.78(s, 1H), 7.11 (s, 1H), 7.28 (d, 1H), 7.75 (s, 1H), 8.13 (s, 1H), 8.42(d, 1H), 9.24 (br, 1H), and 11.40 (br, 1H).

Example 2621-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(9H-purine-6-sulfonylmethyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(9H-purine-6-sulfonylmethyl)-thiazol-2-yl]-urea(78 mg, 74%) was prepared from1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(9H-purin-6-ylsulfanylmethyl)-thiazol-2-yl]-urea(99 mg, 0.20 mmol) and following the general procedure R to give titlecompound.

LC-MS (m/z): 526 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.58 (m, 4H), 1.66(m, 2H), 1.74 (m, 2H), 2.32 (s, 3H), 3.74 (p, 1H), 4.58 (s, 2H), 6.71(d, 1H), 7.06 (d, 1H), 7.16 (s, 1H), 7.42 (d, 1H), 7.72 (br, 1H), 8.18(d, 1H), 8.98 (s, 1H), 9.88 (br, 1H), and 10.26 (br, 1H).

Example 2631-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(pyridin-4-ylsulfanylmethyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(pyridin-4-ylsulfanylmethyl)-thiazol-2-yl]-urea(79 mg, 70%) was prepared from1-(4-chloromethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(94 mg, 0.25 mmol) following the general procedure Q.

LC-MS (m/z): 453 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.68 (m, 4H), 1.86(m, 4H), 2.36 (s, 3H), 3.76 (p, 1H), 4.21 (s, 2H), 6.78 (s, 1H),7.16-7.20 (dd, 2H), 7.34 (d, 1H), 7.70 (s, 1H), 8.13 (s, 1H), 8.38 (dd,1H), 8.42 (d, 1H), 9.46 (br, 1H), and 11.70 (br, 1H).

Example 2641-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(pyridine-4-sulfonylmethyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(pyridine-4-sulfonylmethyl)-thiazol-2-yl]-urea(73 mg, 75%) was prepared from1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-(pyridin-4-ylsulfanylmethyl)-thiazol-2-yl]-urea(90 mg, 0.20 mmol) and following the general procedure R.

LC-MS (m/z): 485 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.66 (m, 4H), 1.86(m, 4H), 2.37 (s, 3H), 3.78 (p, 1H), 4.49 (s, 2H), 6.88 (s, 1H), 7.36(d, 1H), 7.62 (dd, 2H), 7.72 (s, 1H), 8.42 (d, 1H), 8.86 (d, 2H), 9.40(br, 1H), and 11.52 (br, 1H).

Example 265(5-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-tetrazol-1-yl)-aceticacid

(5-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-tetrazol-1-yl)-aceticacid (100 mg, 80%) was prepared from1-(4-chloromethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(94 mg, 0.25 mmol) following the general procedure Q.

LC-MS (m/z): 501 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.74 (m, 4H), 1.90(m, 4H), 2.33 (s, 3H), 3.72 (p, 1H), 4.22 (s, 2H), 5.00 (s, 2H), 6.92(s, 1H), 7.52 (d, 1H), 7.72 (s, 1H), 8.38 (d, 1H), 9.82 (br, 1H), 10.32(br, 1H), and 11.70 (br, 1H).

Example 266(5-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-4-cyclopropyl-4H-[1,2,4]triazol-3-ylmethyl)-carbamic acidtert-butyl ester

(5-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-4-cyclopropyl-4H-[1,2,4]triazol-3-ylmethyl)-carbamic acidtert-butyl ester (136 mg, 89%) was prepared from1-(4-chloromethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(94 mg, 0.25 mmol) following the general procedure Q.

LC-MS (m/z): 612 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.04 (m, 2H), 1.14(m, 2H), 1.40 (s, 9H), 1.66 (m, 4H), 1.84 (m, 4H), 2.35 (s, 3H), 2.88(p, 1H), 3.70 (p, 1H), 4.52 (s, 2H), 4.54 (s, 2H), 5.78 (br, 1H), 6.80(s, 1H), 7.34 (d, 1H), 7.66 (s, 1H), 8.32 (d, 1H), 10.24 (br, 1H), and11.36 (br, 1H).

Example 2671-[4-(5-Aminomethyl-4-cyclopropyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureahydrochloride salt

1-[4-(5-Aminomethyl-4-cyclopropyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(51 mg, 99%) was prepared from(5-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-4-cyclopropyl-4H-[1,2,4]triazol-3-ylmethyl)-carbamic acidtert-butyl ester (61 mg, 0.10 mmol) and hydrochloric acid (4 mL, 4.0 M.in dioxane) following the general deprotection procedure.

LC-MS (m/z): 512 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.24 (m, 2H), 1.38(m, 2H), 1.72 (m, 4H), 1.94 (m, 4H), 2.38 (s, 3H), 2.92 (p, 1H), 3.65(s, 2H), 3.77 (s, 2H), 4.08 (m, 1H), 5.24 (br, 2H), 6.90 (s, 1H), 7.52(d, 1H), 7.72 (s, 1H), 8.42 (d, 1H), 10.24 (br, 1H), and 11.36 (br, 1H).

Example 2682-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-1H-imidazole-4-carboxylicacid ethyl ester

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-1H-imidazole-4-carboxylicacid ethyl ester (112 mg, 88%) was prepared from1-(4-chloromethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(94 mg, 0.25 mmol) following the general procedure Q.

LC-MS (m/z): 486 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.36 (t, 3H), 1.74(m, 4H), 1.90 (m, 4H), 2.36 (s, 3H), 3.78 (p, 1H), 4.08 (q, 2H), 4.34(s, 2H), 6.84 (s, 1H), 7.34 (d, 1H), 7.72 (d, 1H), 7.88 (d, 1H), 8.18(d, 1H), 8.38 (d, 1H), 10.24 (br, 1H), and 11.88 (br, 1H).

Example 2692-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-1H-imidazole-4-carboxylicacid

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-1H-imidazole-4-carboxylicacid (91 mg, 94%) was prepared from2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-1H-imidazole-4-carboxylicacid ethyl ester (102 mg, 0.20 mmol) following the general procedure J.

LC-MS (m/z): 474 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.74 (m, 4H), 1.92(m, 4H), 2.34 (s, 3H), 3.87 (p, 1H), 4.37 (s, 2H), 6.89 (s, 1H), 7.39(d, 1H), 7.68 (d, 1H), 7.84 (d, 1H), 8.15 (d, 1H), 8.26 (d, 1H), 9.28(br, 1H), 10.66 (br, 1H), and 11.90 (br, 1H).

Example 2702-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethanesulfonyl}-1H-imidazole-4-carboxylicacid ethyl ester

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethanesulfonyl}-1H-imidazole-4-carboxylicacid ethyl ester (35 mg, 64%) was prepared from2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-1H-imidazole-4-carboxylicacid ethyl ester (51 mg, 0.10 mmol) following the general procedure R.

LC-MS (m/z): 546 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.42 (t, 3H), 1.63(m, 4H), 1.76 (m, 2H), 1.88 (m, 2H), 2.34 (s, 3H), 3.88 (p, 1H), 4.12(q, 2H), 4.82 (s, 2H), 6.94 (s, 1H), 7.38 (d, 1H), 7.55 (d, 1H), 7.72(d, 1H), 7.91 (d, 1H), 6 (d, 1H), 9.78 (br, 1H), and 11.90 (br, 1H).

Example 2712-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethanesulfonyl}-1H-imidazole-4-carboxylicacid

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethanesulfonyl}-1H-imidazole-4-carboxylicacid (43 mg, 83%) was prepared from2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethanesulfonyl}-1H-imidazole-4-carboxylicacid ethyl ester (52 mg, 0.10 mmol) following the general procedure J.

LC-MS (m/z): 518 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.63 (m, 4H), 1.74(m, 2H), 1.86 (m, 2H), 2.34 (s, 3H), 3.85 (p, 1H), 4.82 (s, 2H), 6.92(s, 1H), 7.38 (d, 1H), 7.54 (d, 1H), 7.72 (d, 1H), 7.90 (s, 1H), 7.96(br, 1H), 8.22 (d, 1H), 10.58 (br, 1H), and 11.88 (br, 1H).

Example 2724-Amino-2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-pyrimidine-5-carboxylicacid ethyl ester

4-Amino-2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-pyrimidine-5-carboxylicacid ethyl ester (113 mg, 84%) was prepared from1-(4-chloromethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(94 mg, 0.25 mmol) following the general procedure Q.

LC-MS (m/z): 541 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.34 (t, 3H), 1.72(m, 4H), 1.88 (m, 4H), 2.34 (s, 3H), 3.62 (br, 2H), 3.74 (p, 1H), 4.10(q, 2H), 4.36 (s, 2H), 6.90 (s, 1H), 7.36 (d, 1H), 7.74 (d, 1H), 8.18(dd, 1H), 8.56 (s, 1H), 10.12 (br, 1H), and 11.78 (br, 1H).

Example 2734-Amino-2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-pyrimidine-5-carboxylicacid

4-Amino-2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-pyrimidine-5-carboxylicacid (94 mg, 91%) was prepared from4-amino-2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-pyrimidine-5-carboxylicacid ethyl ester (108 mg, 0.20 mmol) following the general procedure J.

LC-MS (m/z): 513 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.72 (m, 4H), 1.88(m, 4H), 2.34 (s, 3H), 3.66 (br, 2H), 3.86 (p, 1H), 4.36 (s, 2H), 7.07(s, 1H), 7.32 (d, 1H), 7.72 (d, 1H), 8.20 (dd, 1H), 8.56 (s, 1H), 9.76(br, 1H), 10.64 (br, 1H), and 11.74 (br, 1H).

Example 2742-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-4-hydroxy-pyrimidine-5-carboxylicacid

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-4-hydroxy-pyrimidine-5-carboxylicacid (104 mg, 81%) was prepared from2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-4-hydroxy-pyrimidine-5-carboxylicacid ethyl ester (135 mg, 0.25 mmol) following the general procedure J.

LC-MS (m/z): 514 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 1.74 (m, 4H), 1.90(m, 4H), 2.36 (s, 3H), 3.84 (p, 1H), 4.28 (s, 2H), 6.98 (s, 1H), 7.36(d, 1H), 7.70 (d, 1H), 8.36 (dd, 1H), 8.56 (s, 1H), 9.04 (br, 1H), 9.76(br, 1H), 10.64 (br, 1H), and 11.74 (br, 1H):

Example 2751-[4-(5-Amino-thiazol-2-ylsulfanylmethyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea

1-[4-(5-Amino-thiazol-2-ylsulfanylmethyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(96 mg, 81%) was prepared from1-(4-chloromethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(94 mg, 0.25 mmol) following the general procedure Q.

LC-MS (m/z): 474 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.68 (m, 4H), 1.84(m, 4H), 2.37 (s, 3H), 3.72 (p, 1H), 4.34 (s, 2H), 5.18 (br, 2H), 6.58(s, 1H), 7.16 (s, 1H), 7.36 (d, 1H), 7.64 (s, 1H), 8.26 (d, 1H), 10.56(br, 1H), and 11.60 (br, 1H).

Example 276{2-[3-(2-Cyclopentanecarbonyl-5-methanesulfonylamino-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

{2-[3-(2-Cyclopentanecarbonyl-5-methanesulfonylamino-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (102 mg, 80%) was prepared fromN-(5-amino-4-cyclopentanecarbonyl-2-methyl-phenyl)-methanesulfonamide(198 mg, 0.5 mmol) and ethyl-2-amino-4-thiazolyl acetate (93 mg, 0.5mmol) following the general procedure D.

LC-MS (m/z): 509 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.27 (t, 3H), 1.70(m, 4H), 1.88 (m, 4H), 2.29 (s, 3H), 3.30 (s, 2H), 3.68 (s, 3H), 4.19(q, 2H), 4.24 (p, 1H), 6.48 (s, 1H), 6.72 (s, 1H), 7.74 (s, 1H), 8.64(br, 1H), 9.62 (br, 1H), and 11.82 (br, 1H).

Example 277{2-[3-(2-Cyclopentanecarbonyl-5-methanesulfonylamino-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

{2-[3-(2-Cyclopentanecarbonyl-5-methanesulfonylamino-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (116 mg, 97%) was prepared from{2-[3-(2-cyclopentanecarbonyl-5-methanesulfonylamino-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (127 mg, 0.25 mmol) following the general procedure J.

LC-MS (m/z): 481 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.68 (m, 4H), 1.84(m, 4H), 2.38 (s, 3H), 3.03 (s, 3H), 3.64 (s, 2H), 4.24 (p, 1H), 5.36(br, 1H), 6.50 (s, 1H), 6.78 (s, 1H), 7.68 (s, 1H), 9.62 (br, 1H), 11.24(br, 1H), and 12.54 (br, 1H).

Example 2781-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(1H-imidazol-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(1H-imidazol-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea(25 mg, 50%) was prepared from methanesulfonic acid2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethylester (0.05 g, 0.11 mmol) and 1H-imidazol-2-thiol (0.009 g, 0.11 mmol)following the general procedure Z.

LC/MS (m/z): 456 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) □ 1.63-1.68 (m, 4H),1.83-1.88 (m, 4H), 2.35 (s, 3H), 2.87-2.93 (m, 2H), 3.25-3.28 (m, 2H),3.60-3.75 (m, 1H), 6.74 (s, 1H), 6.85-7.10 (m, 2H), 7.33 (d, 1H), 7.65(s, 1H), 8.4 (d, 1H), 11.35 (br, 1H).

Example 2791-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(1-methyl-1H-imidazol-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(1-methyl-1H-imidazol-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea(45 mg, 43%) was prepared from methanesulfonic acid2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethylester (0.10 g, 0.22 mmol) and 1-methyl-1H-imidazole-2-thiol (0.04 g,0.33 mmol) following the general procedure Z.

LC/MS (m/z): 470 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) □ 1.73-1.76 (m, 4H),1.90-1.93 (m, 4H), 2.36 (s, 3H), 3.04 (t, 2H), 3.35 (t, 2H), 3.6.3 (s,3H), 3.65-3.80 (m, 1H), 6.51 (s, 1H), 6.71 (d, 2H), 7.33 (d, 1H), 7.68(s, 1H), 8.40 (br, 1H), 11.43 (br, 1H).

Example 2801-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(pyridin-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea

1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(pyridin-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea(24 mg, 467%) was prepared from methanesulfonic acid2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethylester (0.05 g, 0.11 mmol) and 2-mercapto pyridine (0.012 g, 0.11 mmol)following the general procedure Z.

LC/MS (m/z): 467 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) □ 1.62-1.74 (m, 4H),1.85-1.93 (m, 4H), 2.36 (s, 3H), 3.05 (t, 2H), 3.50 (t, 2H), 3.72-3.80(m, 1H), 6.54 (s, 1H), 7.13-7.10 (m, 2H), 7.60-7.65 (m, 3H), 8.46-8.49(m, 2H), 11.72 (br, 1H).

Example 2811-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(pyridin-4-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{4-[2-(pyridin-4-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea(74 mg, 60%) was prepared from methanesulfonic acid2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-ethylester (0.12 g, 0.27 mmol) and 2-mercaptopyridine (0.04 g, 0.39 mmol)following the general procedure Z.

LC/MS (m/z): 467 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃) δ 1.69-1.73 (m, 4H),1.87-1.92 (m, 4H), 2.37 (s, 3H), 3.03 (t, 2H), 3.34 (t, 2H), 3.75-3.79(m, 1H), 6.58 (s, 1H), 7.16 (d, 2H), 7.25 (d, 2H), 7.36 (d, 1H), 7.71(s, 1H), 8.46 (d, 1H), 11.74 (s, 1H).

Example 2823-{2-[3-(2-Acetyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-propionicacid

3-(2-Amino-thiazol-4-ylmethylsulfanyl)-propionic acid methyl ester (0.75g, 60%) was prepared from 4-chloromethyl-thiazol-2-ylamine (1.00 g, 5.41mmol) and 3-mercapto-propionic acid methyl ester (0.97 g, 8.11 mmol)according to procedure Z.

3-{2-[3-(2-Acetyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-propionicacid methyl ester (0.28 g, 61%) was prepared from3-(2-amino-thiazol-4-ylmethylsulfanyl)-propionic acid methyl ester (0.23g, 0.99 mmol) and (2-amino-5-methyl-phenyl)-cyclopentyl-methanone (0.24g, 1.49 mmol) following the procedure D.

3-{2-[3-(2-Acetyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethylsulfanyl}-propionicacid (40 mg, 83%) was prepared from[4-(2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}ethoxy)-phenyl]aceticacid methyl ester (0.05 g, 0.11 mmol) and 2.5M LiOH (20 uL) followingthe general procedure J.

LC/MS (m/z): 448 (M+1)⁺; ¹H NMR (400 MHz, DMSO) □ 1.70-1.80 (m, 4H),1.85-1.97 (m, 4H), 2.28 (s, 3H), 2.67 (t, 2H), 2.83 (t, 2H), 3.70 (s,2H), 3.85-3.90 (m, 1H), 6.89 (s, 1H), 7.20 (d, 2H), 7.85 (s, 1H), 8.20(d, 1H), 10.64 (br, 1H), 10.73 (br, 1H), 12.14 (br, 1H).

Example 2831-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-methylsulfanyl-thiazol-2-yl)-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-methylsulfanyl-thiazol-2-yl)-urea(94 mg, 25%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and sodiummethanethiolate (140 mg, 2 mmol) following the general procedure Q.

LC-MS (m/z): 376 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.74 (m, 4H), 1.93(m, 4H) 2.38 (s, 3H), 2.43 (s, 3H), 3.79 (m, 1H), 7.37 (d, 1H), 7.73 (s,2H), 8.45 (d, 1H), 11.65 (br, 1H), 12.20 (br, 1H).

Example 284{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-aceticacid methyl ester

{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-aceticacid methyl ester (130 mg, 30%) was prepared from1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol), andmercapto-acetic acid methyl ester (212 mg, 2 mmol) following the generalprocedure Q.

LC-MS (m/z): 434 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.71 (m, 4H), 1.91(m, 4H), 2.38 (s, 3H), 3.47 (s, 3H), 3.72 (s, 3H), 3.79 (m, 1H), 7.39(d, 1H), 7.75 (d, 2H), 8.43 (d, 1H), 11.40 (br, 1H), 11.66 (br, 1H).

Example 285{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-aceticacid

{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-aceticacid (161 mg, 75%) was prepared from{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-aceticacid methyl ester (229 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 420 (M+1)⁺: ¹H NMR (400 MHz, DMSO-d): δ 1.61 (m, 4H), 1.74(m, 2H) 1.89 (m, 2H), 2.33 (s, 3H), 3.49 (s, 3H), 3.88 (m, 1H), 7.41 (d,2H), 7.92 (d, 1H), 8.33 (d, 1H), 10.80 (br, 1H), 10.98 (br, 1H), 12.12(br, 1H).

Example 286{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-sulfonyl}-aceticacid methyl ester

(2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-sulfonyl)-aceticacid methyl ester (175 mg, 75%) was prepared from{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-sulfanyl}-aceticacid methyl ester (217 mg, 0.5 mmol) by oxidation with m-cpba followingthe general procedure R.

LC-MS (m/z): 466 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.71 (m, 4H), 1.91(m, 4H), 2.38 (s, 3H), 3.78 (m, 4H), 4.24 (s, 2H), 7.41 (d, 1H), 7.77(s, 1H), 8.30 (s, 1H), 8.42 (d, 1H), 11.89 (br, 1H).

Example 287{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-sulfonyl}-aceticacid

{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-aceticacid (158 mg, 70%) was prepared from{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-aceticacid methyl ester (233 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 452 (M+1)⁺; ¹H NMR (400 MHz, acetone-d₆): δ 1.67 (m, 4H),1.71 (m, 4H), 1.91 (m, 4H), 2.38 (s, 3H), 3.95 (m, 1H), 4.44 (s, 2H),7.44 (d, 1H), 7.97 (s, 2H), 8.42 (d, 1H), 11.15 (br, 1H), 11.35 (br,1H).

Example 2883-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-propionicacid methyl ester

{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-propionicacid methyl ester (125 mg, 28%) was prepared from1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol), andmercapto-propionic acid methyl ester (240 mg, 2 mmol) following thegeneral procedure Q.

LC-MS (m/z): 448 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.71 (m, 4H), 1.91(m, 4H), 2.38 (s, 3H), 2.65 (s, 2H), 3.51 (s, 2H), 3.66 (s, 3H), 3.78(m, 1H), 6.90 (d, 1H), 7.38 (d, 1H), 7.73 (s, 1H), 8.42 (d, 1H) 11.62(br, 1H), 11.65 (br, 1H).

Example 2893-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-propionicacid

{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-propionicacid (138 mg, 72%) was prepared from{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-propionicacid methyl ester (217 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 433 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.67 (m, 4H), 1.89(m, 4H), 2.36 (s, 3H), 2.51 (s, 2H), 3.59 (s, 2H), 3.78 (m, 1H), 6.90(d, 1H), 7.41 (d, 1H), 7.93 (s, 1H), 8.45 (d, 1H), 9.56 (br, 1H), 11.16(br, 1H), 11.25 (br, 1H).

Example 2903-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-sulfonyl}-propionicacid methyl ester

{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-sulfonyl}-propionicacid methyl ester (163 mg, 68%) was prepared from{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-sulfanyl}-propionicacid methyl ester (224 mg, 0.5 mmol) by oxidation with m-cpba followingthe general procedure R.

LC-MS (m/z): 480 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.71 (m, 6H), 1.91(m, 2H), 2.40 (s, 3H), 2.85 (m, 2H), 3.56 (m, 2H), 3.67 (s, 3H), 3.81(m, 1H), 7.41 (dd, 1H), 7.78 (s, 2H), 8.29 (s, 1H), 8.42 (d, 1H), 11.40(br, 1H), 11.91 (br, 1H).

Example 2913-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-sulfonyl}-propionicacid

{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-propionicacid (168 mg, 72%) was prepared from{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-propionicacid methyl ester (240 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 466 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.71 (m, 4H), 1.91(m, 4H), 2.38 (s, 3H), 2.89 (s, 2H), 3.63 (s, 2H), 3.81 (m, 1H), 7.39(d, 1H), 7.75 (d, 2H), 8.43 (d, 1H), 11.40 (br, 1H), 11.66 (br, 1H).

Example 292N-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl-sulfanyl}-ethyl)-acetamide

N-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl-sulfanyl}-ethyl)-acetamide(156 mg, 35%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol), andN-(2-mercapto-ethyl)-acetamide (240 mg, 2 mmol) following the generalprocedure Q.

LC-MS (m/z): 447 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.71 (m, 4H), 1.91(m, 4H), 1.99 (s, 3H), 2.38 (s, 3H), 2.85 (t, 3H), 3.46 (q, 2H), 3.79(m, 1H), 5.95 (br, 1H), 7.37 (d, 1H), 7.69 (d, 2H), 8.42 (d, 1H), 11.35(br, 1H), 11.57 (br, 1H).

Example 293N-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl-sulfonyl}-ethyl)-acetamide

N-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl-sulfonyll}-ethyl)-acetamide(167 mg, 70%) was prepared fromN-(2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl-sulfanyl}-ethyl)-acetamide(223 mg, 0.5 mmol) by oxidation with m-cpba following the generalprocedure R.

LC-MS (m/z): 479 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.70 (m, 4H), 1.92(m, 4H), 2.01 (s, 3H), 2.39 (s, 3H), 3.42 (m, 2H), 3.76 (m, 3H), 6.32(m, 1H), 7.39 (d, 1H), 7.76 (s, 2H), 8.13 (s, 1H), 8.40 (d, 1H), 11.66(br, 1H).

Example 2942-Acetylamino-3-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-propionicacid methyl ester

2-Acetylamino-3-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-propionicacid methyl ester (156 mg, 35%) was prepared from1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and2-acetylamino-3-mercapto-propionic acid methyl ester (354 mg, 2 mmol)following the general procedure Q.

LC-MS (m/z): 505 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.71 (m, 6H), 1.91(m, 2H), 2.03 (s, 3H), 2.38 (s, 3H), 3.24 (m, 2H), 3.66 (s, 3H), 3.79(m, 1H), 4.84 (m, 1H), 6.42 (d, 1H), 7.39, d, 1H), 7.60 (s, 1H), 7.73(s, 1H), 8.43 (d, 1H), 10.88 (br, 1H), 11.64 (br, 1H).

Example 2952-Acetylamino-3-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-propionicacid

2-Acetylamino-3-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-propionicacid (187 mg, 76%) was prepared from2-acetylamino-3-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-propionicacid methyl ester (245 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 491 (M+1)⁺; ¹H NMR (400 MHz, Acetone-d₆): δ 1.68 (m, 4H),1.84 (m, 4H), 1.97 (s, 3H), 2.37 (s, 3H), 3.10 (m, 1H), 3.26 (m, 1H),3.94 (m, 1H), 4.64 (m, 1H), 5.8 (br, 1H), 7.45 (d, 1H), 7.54 (d, 1H),8.01 (s, 1H), 8.43 (d, 1H), 11.20 (br, 1H), 11.44 (br, 1H).

Example 2962-tert-Butoxycarbonylamino-3-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]thiazol-5-ylsulfanyl}-propionicacid methyl ester

2-tert-Butoxycarbonylamino-3-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]thiazol-5-ylsulfanyl}-propionicacid methyl ester (196 mg, 35%) was prepared from1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and2-tert-butoxycarbonylamino-3-mercapto-propionic acid methyl ester (470mg, 2 mmol) following the general procedure Q.

LC-MS (m/z): 563 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.55 (s, 9H), 1.71(m, 4H), 1.91 (m, 4H), 2.37 (s, 3H), 3.18 (m, 2H), 3.76 (m, 4H), 4.53(m, 1H), 5.45 (m, 1H), 7.35 (d, 1H), 7.65 (s, 1H), 7.72 (s, 1H), 8.43(d, 1H), 11.60 (br, 1H), 11.66 (br, 1H).

Example 297(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-ethyl)-carbamicacid tert-butyl ester

(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-ethyl)-carbamicacid tert-butyl ester (202 mg, 40%) was prepared from1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and(2-mercapto-ethyl)-carbamic acid tert-butyl ester (354 mg, 2 mmol)following the general procedure Q.

LC-MS (m/z): 505 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.45 (s, 9H), 1.71(m, 4H), 1.92 (m, 4H), 2.38 (s, 3H), 2.83 (m, 2H), 3.32 (m, 2H), 3.78(m, 1H), 4.95 (br, 1H), 7.36 (d, 1H), 7.73 (s, 2H), 8.43 (d, 1H), 11.48(br, 1H), 11.62 (br, 1H).

Example 2982-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-ethyl-ammonium;chloride

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-ethyl-ammonium;chloride (183 mg, 90%) was prepared by reacting(2-{2-[3-(2-cyclopentane-carbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-ethyl)-carbamicacid tert-butyl ester (253 mg, 0.5 mmol) with 4 N HCl in dioxane LC-MS(m/z): 406 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.63 (m, 4H), 1.73 (m,2H), 1.91 (m, 2H), 2.33 (s, 3H), 2.91 (m, 2H), 3.18 (m, 2H), 3.87 (m,1H), 7.39 (d, 1H), 7.56 (s, 2H), 7.85 (s, 1H), 8.16 (d, 1H), 10.71 (br,1H), 12.20 (br, 1H).

Example 299(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-sulfonyl}-ethyl)carbamicacid tert-butyl ester

(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-sulfonyl}-ethyl)-carbamicacid tert-butyl ester (195 mg, 73%) was prepared from(2-{2-[3-(2-cyclopentane-carbonyl-4-methyl-phenyl)-ureido]-thiazole-5-sulfanyl}-ethyl)carbamicacid tert-butyl ester (252 mg, 0.5 mmol) by oxidation with m-cpbafollowing the general procedure R.

LC-MS (m/z): 537 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.44 (s, 9H), 1.71(m, 4H), 1.91 (m, 4H), 2.38 (s, 3H), 3.46 (t, 2H), 3.78 (m, 3H), 3.81(m, 1H), 7.39 (d, 1H), 7.75 (d, 2H), 8.43 (d, 1H), 11.40 (br, 1H), 11.66(br, 1H).

Example 3002-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-sulfonyl}-ethylammonium; chloride

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-ethyl-ammonium;chloride (185 mg, 85%) was prepared by reacting(2-{2-[3-(2-cyclopentane-carbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-ethyl)-carbamicacid tert-butyl ester (253 mg, 0.5 mmol) with 4 N HCl in dioxane LC-MS(m/z): 438 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.61 (m, 4H), 1.72 (m,2H), 1.88 (m, 2H), 2.34 (s, 3H), 3.01 (br, 2H), 3.70 (t, 2H), 3.88 (m,1H), 7.41 (d, 1H), 7.87 (s, 1H), 8.13 (d, 1H), 8.15 (br, 1H), 10.75 (br,1H), 11.62 (br, 1H).

Example 3011-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(2-dimethylamino-ethylsulfanyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(2-dimethylamino-ethylsulfanyl)-thiazol-2-yl]-urea(130 mg, 30%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and2-dimethylamino-ethanethiol (210 mg, 2 mmol) following the generalprocedure Q.

LC-MS (m/z): 433 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.71 (m, 4H), 1.92(m, 4H), 2.24 (s, 6H), 2.38 (s, 3H), 2.55 (m, 2H), 2.83 (m, 2H), 3.78(m, 1H), 7.36 (d, 1H), 7.69 (s, 1H), 7.74 (s, 1H), 8.44 (d, 1H), 11.65(br, 1H).

Example 3021-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(2-hydroxy-ethylsulfanyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(2-hydroxy-ethylsulfanyl)-thiazol-2-yl]-urea(114 mg, 28%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and2-hydroxy-ethanethiol (158 mg, 2 mmol) following the general procedureQ.

LC-MS (m/z): 406 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃/acetone-d₆): δ 1.52 (m,4H), 1.68 (m, 2H), 1.75 (m, 2H), 2.33 (s, 3H), 2.71 (t, 3H), 3.58 (m,2H), 3.90 (m, 1H), 7.17 (d, 1H), 7.31 (s, 1H), 7.56 (s, 1H), 8.27 (d,1H), 11.20 (br, 1H).

Example 3031-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(2-hydroxy-ethylsulfonyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(2-hydroxy-ethylsulfonyl)-thiazol-2-yl]-urea(153, 70%) was prepared from1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(2-hydroxy-ethylsulfanyl)-thiazol-2-yl]-urea(204 mg, 0.5 mmol) by oxidation with m-cpba following the generalprocedure R.

LC-MS (m/z): 438 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃/acetone-d₆): δ 1.66 (m,4H), 1.89 (m, 4H), 2.37 (s, 3H), 3.48 (m, 2H), 3.72 (m, 2H), 4.07 (m,2H), 7.37 (d, 1H), 7.54 (d, 1H), 7.66 (d, 1H), 8.01 (d, 1H), 11.88 (br,1H).

Example 3041-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea(140 mg, 32%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and2-mercaptopyridine (222 mg, 2 mmol) following the general procedure Q.

LC-MS (m/z): 439 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.63 (m, 4H), 1.86(m, 4H), 2.37 (s, 3H), 3.76 (m, 1H), 7.04 (m, 2H), 7.37 (d, 1H), 7.51(m, 1H), 7.73 (s, 1H), 7.92 (s, 1H), 8.42 (d, 1H), 8.48 (d, 1H), 11.16(br, 1H), 11.81 (br, 1H).

Example 3051-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea(176 mg, 75%) was prepared from1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-sulfanyl)-thiazol-2-yl]-urea(219 mg, 0.5 mmol) by oxidation with m-cpba following the generalprocedure R.

LC-MS (m/z): 471 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.68 (m, 4H), 1.93(m, 4H), 2.39 (s, 3H), 3.79 (m, 1H), 7.39 (d, 1H), 7.48 (m, 1H), 7.76(s, 1H), 7.93 (dd, 1H), 8.15 (d, 1H), 8.33 (br, 1H), 8.42 (d, 1H), 8.70(d, 1H), 10.8 (br, 1H), 11.93 (br, 1H).

Example 3061-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyrimidin-2-ylsulfanyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyrimidin-2-ylsulfanyl)-thiazol-2-yl]-urea(142 mg, 32%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and2-mercaptopyrimidine (222 mg, 2 mmol) following the general procedure Q.

LC-MS (m/z): 440 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.64 (m, 4H), 1.89(m, 4H), 2.36 (s, 3H), 3.81 (m, 1H), 7.01 (t, 1H), 7.34 (d, 2H), 7.72(s, 1H), 7.87 (s, 1H), 8.47 (d, 1H), 8.58 (d, 1H), 8.67 (d, 1H), 11.70(br, 1H), 11.78 (br, 1H).

Example 3071-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyrimidin-2-ylsulfonyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyrimidine-2-sulfonyl)-thiazol-2-yl]-urea(169 mg, 72%) was prepared from1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyrimidine-2-sulfanyl)-thiazol-2-yl]-urea(220 mg, 0.5 mmol) by oxidation with m-cpba following the generalprocedure R.

LC-MS (m/z): 472 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.71 (m, 4H), 1.91(m, 4H), 2.38 (s, 3H), 3.78 (m, 1H), 7.39 (d, 1H), 7.49 (t, 1H), 7.76(s, 1H), 8.31 (s, 1H), 8.43 (d, 1H), 8.93 (d, 2H), 11.80 (br, 1H), 11.94(br, 1H).

Example 3081-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridin-4-ylsulfanyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridin-4-ylsulfanyl)-thiazol-2-yl]-urea(110 mg, 25%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and4-mercaptopyridine (222 mg, 2 mmol) following the general procedure Q.

LC-MS (m/z): 439 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.62 (m, 4H), 1.84(m, 4H), 2.35 (s, 3H), 3.73 (m, 1H), 7.10 (d, 2H), 7.34 (d, 2H), 7.71(s, 1H), 7.95 (s, 1H), 8.38 (d, 1H), 8.42 (d, 1H), 11.65 (br, 1H), 11.75(br, 1H).

Example 3091-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1-methyl-1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1-methyl-1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea(141 mg, 32%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and1-methyl-1H-imidazole-2-thiol (228 mg, 2 mmol) following the generalprocedure Q.

LC-MS (m/z): 442 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.66 (m, 4H), 1.88(m, 4H), 2.35 (s, 3H), 3.74 (m, 1H), 3.77 (s, 3H), 6.93 (s, 1H), 7.06(s, 1H), 7.32 (d, 1H), 7.69 (s, 1H), 7.82 (s, 1H), 8.40 (d, 1H), 11.51(br, 1H), 12.20 (br, 1H).

Example 3101-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea(149 mg, 35%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and1H-imidazole-2-thiol (200 mg, 2 mmol) following the general procedure Q.

LC-MS (m/z): 428 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.70 (m, 4H), 1.91(m, 4H), 2.37 (s, 3H), 3.83 (m, 1H), 7.10 (s, 1H), 7.34 (d, 1H), 7.57(s, 2H), 7.66 (s, 1H), 7.78 (s, 1H), 8.42 (d, 1H), 11.22 (br, 1H).

Example 3111-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(7H-purin-6-ylsulfanyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(7H-purin-6-ylsulfanyl)-thiazol-2-yl]-urea(124 mg, 28%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and7H-purine-6-thiol (304 mg, 2 mmol) following the general procedure Q.

LC-MS (m/z): 480 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.61 (m, 4H), 1.81(m, 4H), 2.26 (s, 3H), 3.64 (m, 1H), 7.21 (d, 2H), 7.54 (d, 2H), 8.02(s, 1H), 8.26 (d, 1H), 8.56 (s, 1H), 11.12 (br, 1H), 11.62 (br, 1H).

Example 3122-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-nicotinicacid methyl ester

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-nicotinicacid methyl ester (124 mg, 25%) was prepared from1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and2-mercapto-nicotinic acid methyl ester (340 mg, 2 mmol) following thegeneral procedure O.

LC-MS (m/z): 497 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.64 (m, 4H), 1.85(m, 4H), 2.36 (s, 3H), 3.74 (m, 1H), 3.98 (s, 3H), 7.08 (dd, 1H), 7.34(d, 2H), 7.71 (s, 1H), 7.79 (s 1H), 8.22 (dd, 1H), 8.45 (d, 1H), 8.49(dd, 1H), 11.45 (br, 1H), 11.75 (br, 1H).

Example 3132-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-nicotinicacid

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-nicotinicacid (186 mg, 75%) was prepared from2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-nicotinicacid methyl ester (248 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 483 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.62 (m, 4H), 1.75(m, 2H), 1.89 (m, 2H), 2.33 (s, 3H), 3.88 (m, 1H), 7.23 (dd, 1H), 7.39(d, 1H), 7.47 (s, 1H), 7.86 (s, 1H), 8.19 (m, 2H), 8.24 (dd, 1H), 10.70(br, 1H), 12.23 (br, 1H)

Example 3142-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-nicotinicacid methyl ester

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-nicotinicacid methyl ester (185 mg, 70%) was prepared from2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-nicotinicacid methyl ester (248 mg, 0.5 mmol) by oxidation with m-cpba followingthe general procedure R.

LC-MS (m/z): 529 (M+1)⁺, ¹H NMR (400 MHz, CDCl₃): δ 1.68 (m, 4H), 1.85(m, 2H), 1.95 (m, 2H), 2.38 (s, 3H), 3.95 (m, 1H), 3.99 (s, 3H), 7.42(d, 1H), 7.79 (dd, 2H), 7.97 (s, 1H), 8.14 (s, 1H), 8.15 (d, 1H), 8.82(d, 1H), 8.79 (d, 1H), 11.35 (br, 1H), 11.68 (br, 1H).

Example 3152-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-nicotinicacid

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-nicotinicacid (200 mg, 78%) was prepared from2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-nicotinicacid methyl ester (264 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 515 (M+1)⁺; ¹H NMR (400 MHz, acetone-d₆): δ 1.67 (m, 4H),1.84 (m, 2H), 1.95 (m, 2H), 2.38 (s, 3H), 3.95 (m, 1H), 7.44 (d, 1H),7.76 (dd, 1H), 7.96 (s, 1H), 8.05 (s, 1H), 8.18 (d, 1H), 8.42 (d, 1H),8.77 (d, 1H), 11.23 (br, 1H), 11.36 (br, 1H).

Example 3166-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-nicotinicacid methyl ester

6-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-nicotinicacid methyl ester (100 mg, 20%) was prepared from1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and6-mercapto-nicotinic acid methyl ester (340 mg, 2 mmol) following thegeneral procedure Q.

LC-MS (m/z): 497 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.64 (m, 4H), 1.85(m, 4H), 2.33 (s, 3H), 3.79 (m, 1H), 3.99 (s, 3H), 7.10 (dd, 1H), 7.34(dd, 1H), 7.71 (s, 1H), 7.79 (s 1H), 8.22 (dd, 1H), 8.45 (d, 1H), 8.50(dd, 1H), 8.79 (s, 1H), 11.50 (br, 1H), 11.75 (br, 1H).

Example 3176-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-nicotinicacid

6-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-nicotinicacid (169 mg, 70%) was prepared from6-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-nicotinicacid methyl ester (248 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 483 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.62 (m, 4H), 1.75(m, 2H), 1.89 (m, 2H), 2.33 (s, 3H), 3.89 (m, 1H), 7.12 (d, 1H), 7.38(d, 1H), 7.75 (s, 1H), 7.87 (s, 1H), 8.12 (dd, 2H), 8.24 (dd, 1H), 8.85(s, 1H), 10.76 (br, 1H), 12.60 (br, 1H).

Example 3186-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-nicotinicacid methyl ester

6-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-nicotinicacid methyl ester (172 mg, 65%) was prepared from6-{2-[3-(2-cyclopentane-carbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-nicotinicacid methyl ester (248 mg, 0.5 mmol) by oxidation with m-cpba followingthe general procedure R.

LC-MS (m/z): 529 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.74 (m, 4H), 1.97(m, 4H), 2.38 (s, 3H), 3.81 (m, 1H), 3.98 (s, 3H), 7.44 (t, 1H), 7.58(d, 1H), 8.02 (dd, 1H), 8.11 (s, 1H), 8.23 (d, 1H), 8.52 (dd, 1H), 9.26(d, 1H), 10.56 (br, 1H), 12.11 (br, 1H).

Example 3193-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-pyridine-2-carboxylicacid methyl ester

3-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-pyridine-2-carboxylicacid methyl ester (149 mg, 30%) was prepared from1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and3-mercapto-pyridine-2-carboxylic acid methyl ester (340 mg, 2 mmol)following the general procedure Q.

LC-MS (m/z): 497 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.59 (m, 4H), 1.80(m, 2H), 1.91 (m, 2H), 2.37 (s, 3H), 3.73 (m, 1H), 4.01 (s, 3H), 7.29(dd, 1H), 7.36 (d, 1H), 7.52 (dd, 1H), 7.72 (s, 1H), 7.97 (s, 1H), 8.11(dd, 1H), 8.46 (m, 1H), 11.83 (br, 1H).

Example 3203-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-pyridine-2-carboxylicacid

3-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-pyridine-2-carboxylicacid (181 mg, 75%) was prepared from3-{2-[3-(2-Cyclopentane-carbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-pyridine-2-carboxylicacid methyl ester (248 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 483 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.62 (m, 4H), 1.75(m, 2H), 1.91 (m, 2H), 2.32 (s, 3H), 3.88 (m, 1H), 7.38 (d, 2H), 7.51(dd, 1H), 7.72 (s, 1H), 7.87 (s, 1H), 8.13 (d, 1H), 8.44 (d, 1H), 10.74(br, 1H), 12.25 (br, 1H).

Example 3212-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-1H-imidazole-4-carboxylicacid ethyl ester

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-1H-imidazole-4-carboxylicacid ethyl ester (190 mg, 38%) was prepared from1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and 2-mercapto-1H-imidazole-4-carboxylic acid ethyl ester (340 mg, 2 mmol) following thegeneral procedure Q.

LC-MS (m/z): 500 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.27 (t, 3H), 1.62(m, 4H), 1.72 (m, 2H), 1.89 (m, 2H), 2.34 (s, 3H), 3.87 (m, 1H), 4.16(q, 2H), 6.60 (br, 1H), 7.39 (d, 1H), 7.70 (s, 1H), 7.82 (s, 2H), 8.15(d, 1H), 10.22 (br, 1H), 11.90 (br, 1H).

Example 3222-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-1H-imidazole-4-carboxylicacid

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-1H-imidazole-4-carboxylicacid (167 mg, 71%) was prepared from2-{2-[3-(2-cyclopentane-carbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-1H-imidazole-4-carboxylicacid ethyl ester (250 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 472 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.61 (m, 4H), 1.73(m, 2H), 1.89 (m, 2H), 2.33 (s, 3H), 3.87 (m, 1H), 6.53 (br, 1H), 7.37(d, 1H), 7.64 (s, 1H), 7.83 (s, 2H), 8.14 (d, 1H), 10.70 (br, 1H), 12.20(br, 1H).

Example 3232-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-1H-imidazole-4-carboxylicacid ethyl ester

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-1H-imidazole-4-carboxylicacid ethyl ester (181 mg, 68%) was prepared from2-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-1H-imidazole-4-carboxylicacid ethyl ester (250 mg, 0.5 mmol) by oxidation with m-cpba followingthe general procedure R.

LC-MS (m/z): 532 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.27 (t, 3H), 1.71(m, 4H), 1.91 (m, 4H), 2.36 (s, 3H), 3.73 (m, 1H), 4.38 (q, 2H), 6.98(s, 1H), 7.34 (d, 1H), 7.71 (s, 1H), 7.83 (s, 1H), 8.22 (br, 1H), 8.38(d, 1H), 11.80 (br, 1H).

Example 3242-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-1H-imidazole-4-carboxylicacid

2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-1H-imidazole-4-carboxylicacid (171 mg, 68%) was prepared from2-{2-[3-(2-cyclopentane-carbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfonyl}-1H-imidazole-4-carboxylicacid ethyl ester (266 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 504 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.61 (m, 4H), 1.75(m, 2H), 1.89 (m, 2H), 2.33 (s, 3H), 3.88 (m, 1H), 7.41 (d, 1H), 7.53(dd, 2H), 7.69 (dd, 1H), 7.88 (m, 1H), 8.01 (br, 1H), 8.14 (d, 1H),10.86 (br, 1H).

Example 325(3-Cyclopentanecarbonyl-4-{3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-ureido}-phenyl)-aceticacid ethyl ester

(3-Cyclopentanecarbonyl-4-{3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-ureido}-phenyl)-aceticacid ethyl ester (153 mg, 30%) was prepared from{4-[3-(5-bromo-thiazol-2-yl)-ureido]-3-cyclopentanecarbonyl-phenyl}-aceticacid ethyl ester (480 mg, 1 mmol) and 2-mercapto-pyridine (222 mg, 2mmol) following the general procedure Q.

LC-MS (m/z): 511 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.26 (t, 3H), 1.61(m, 4H), 1.85 (m, 4H), 3.62 (s, 2H), 3.76 (m, 1H), 4.16 (q, 2H), 7.01(dd, 1H), 7.06 (d, 1H), 7.45 (d, 1H), 7.51 (d, 1H), 7.89 (s, 1H), 7.93(s, 1H), 8.41 (dd, 1H), 8.55 (d, 1H), 11.70 (br, 1H), 11.89 (br, 1H).

Example 326(3-Cyclopentanecarbonyl-4-{3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-ureido}-phenyl)-aceticacid

(3-Cyclopentanecarbonyl-4-{3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-ureido}-phenyl)-aceticacid (173 mg, 72%) was prepared from(3-cyclopentanecarbonyl-4-{3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-ureido}-phenyl)-aceticacid ethyl ester (255 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 483 (M+1)⁺; ¹H NMR (400 MHz, Acetone d₆): δ 1.64 (m, 4H),1.86 (m, 2H), 1.98 (m, 4H), 3.71 (s, 2H), 3.94 (m, 1H), 7.08 (d, 1H),7.15 (dd, 1H), 7.53 (d, 1H), 7.61 (s, 1H), 7.68 (m, 1H), 8.11 (s, 1H),8.39 (m, 1H), 8.52 (d, 1H), 11.30 (br, 1H), 11.35 (br, 1H).

Example 327(3-Cyclopentanecarbonyl-4-{3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-ureido}-phenyl)aceticacid ethyl ester

(3-Cyclopentanecarbonyl-4-{3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-ureido}-phenyl)aceticacid ethyl ester (120 mg, 24%) was prepared from{4-[3-(5-bromo-thiazol-2-yl)-ureido]-3-cyclopentanecarbonyl-phenyl}-aceticacid ethyl ester (480 mg, 1 mmol) and 1H-imidazole-2-thiol (200 mg, 2mmol) following the general procedure Q.

LC-MS (m/z): 500 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.21 (t, 3H), 1.58(m, 4H), 1.83 (m, 4H), 3.61 (m, 3H), 4.17 (q, 1H), 6.73 (s, 1H), 7.04(m, 2H), 7.38 (d, 1H), 7.61 (br, 1H), 7.81 (s, 1H), 8.41 (d, 1H), 11.23(br, 1H), 11.49 (br, 1H).

Example 328(3-Cyclopentanecarbonyl-4-{3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-ureido}-phenyl)-aceticacid

(3-Cyclopentanecarbonyl-4-{3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-ureido}-phenyl)-aceticacid (177 mg, 72%) was prepared from(3-cyclopentanecarbonyl-4-{3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-ureido}-phenyl)-aceticacid ethyl ester (250 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 472 (M+1)⁺; ¹H NMR (400 MHz, acetone d₆): δ 1.61 (m, 4H),1.91 (m, 4H), 3.58 (s, 2H), 3.72 (m, 1H), 6.77 (s, 1H), 7.04 (d, 1H),7.33 m, 2H), 7.64 (br, 1H), 7.80 (s, 1H), 8.43 (d, 1H), 11.44 (br, 1H),11.59 (br, 1H).

Example 3291-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-2-yl]-urea(133 mg, 30%) was prepared from1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(408 mg, 1 mmol) and 1-methyl-1H-tetrazole-5-thiol (202 mg, 2 mmol)following the general procedure Y

LC-MS (m/z): 444 (M+1)⁺, ¹H NMR (400 MHz, CDCl₃): δ 1.70 (m, 4H), 1.91(m, 4H), 2.37 (s, 3H), 3.78 (m, 1H), 4.06 (s, 3H), 7.37 (d, 1H), 7.73(s, 1H), 7.93 (s, 1H), 8.41 (d, 1H), 9.30 (br, 1H), 11.74 (br, 1H).

Example 330(5-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-tetrazol-1-yl)-aceticacid

(5-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-tetrazol-1-yl)-aceticacid (136 mg, 28%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and(5-mercapto-tetrazol-1-yl)-acetic acid (320 mg, 2 mmol) following thegeneral procedure Y.

LC-MS (m/z): 488 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 1.70 (m, 4H), 1.91(m, 4H), 2.34 (s, 3H), 3.89 (m, 1H), 5.48 (s, 2H), 7.42 (d, 1H), 7.81(s, 1H), 7.88 (s, 1H), 8.17 (d, 1H), 10.76 (br, 1H), 12.25 (br, 2H).

Example 3311-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanyl]-thiazol-2-yl}-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanyl]-thiazol-2-yl}-urea(125 mg, 25%) was prepared from1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(408 mg, 1 mmol) and 1-(2-dimethylamino-ethyl)-1H-tetrazole-5-thiol (346mg, 2 mmol) following the general procedure Y

LC-MS (m/z): 501 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 1.70 (m, 4H), 1.91(m, 4H), 2.28 (s, 6H), 2.34 (s, 3H), 2.76 (t, 2H), 3.74 (m, 1H), 4.42(t, 2H), 7.32 (d, 1H), 7.68 (s, 1H), 7.83 (s, 1H), 8.36 (d, 1H), 11.25(br, 1H), 11.40 (br, 1H).

Example 3321-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(4H-[1,2,4]triazol-3-ylsulfanyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(4H-[1,2,4]triazol-3-ylsulfanyl)-thiazol-2-yl]-urea(129 mg, 30%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and2H-[1,2,4]triazole-3-thiol (202 mg, 2 mmol) following the generalprocedure Y

LC-MS (m/z): 429 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 1.63 (m, 4H), 1.70(m, 2H), 1.91 (m, 2H), 2.34 (s, 3H), 3.89 (m, 1H), 7.41 (d, 1H), 7.63(s, 1H), 7.87 (s, 1H), 8.17 (d, 1H), 10.72 (br, 1H), 12.18 (br, 1H).

Example 3331-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-thiazol-2-yl]-urea(125 mg, 25%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and4-methyl-4H-[1,2,4]triazole-3-thiol (230 mg, 2 mmol) following thegeneral procedure Y

LC-MS (m/z): 443 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 1.63 (m, 4H), 1.75(m, 2H), 1.91 (m, 1H), 2.34 (s, 3H), 3.70 (s, 3H), 3.89 (m, 1H), 7.41(d, 1H), 7.73 (s, 1H), 7.87 (s, 1H), 8.16 (d, 1H), 8.62 (s, 1H), 10.72(br, 1H), 12.15 (br, 1H).

Example 3341-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4]triazole-3-sulfonyl)-thiazol-2-yl]-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4]triazole-3-sulfonyl)-thiazol-2-yl]-urea(171 mg, 72%) was prepared from1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4]triazole-3-sulfanyl)-thiazol-2-yl]-urea(221 mg, 0.5 mmol) by oxidation with m-cpba following the generalprocedure R

LC-MS (m/z): 475 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 1.73 (m, 4H), 1.85(m, 2H), 1.91 (m, 2H), 2.34 (s, 3H), 3.70 (s, 3H), 3.89 (m, 1H), 7.51(d, 1H), 7.73 (s, 1H), 7.87 (s, 1H), 8.16 (d, 1H), 8.62 (s, 1H), 10.72(br, 1H), 12.15 (br, 1H).

Example 335(4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-phenyl)-acetic acid

(4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-phenyl)-acetic acid (140 mg, 30%) was prepared from1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol) and(4-mercapto-phenyl)-acetic acid (336 mg, 2 mmol) following the generalprocedure Y.

(LC-MS (m/z): 496 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.63 (m, 4H),1.75 (m, 2H), 1.91 (m, 2H), 2.33 (s, 3H), 3.59 (s, 2H), 3.89 (m, 1H),7.20 (m, 3H), 7.40 (d, 2H), 7.68 (s, 1H), 7.87 (s, 1H), 8.16 (d, 1H),12.36 (br, 3H).

Example 3361-(5-Acetyl-4-methyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea

1-(5-Acetyl-4-methyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(116 mg, 60%) was prepared from(2-amino-5-methyl-phenyl)-cyclopentyl-methanone (102 mg, 0.5 mmol) and1-(2-amino-4-methyl-thiazol-5-yl)-ethanone (94 mg, 0.6 mmol) followingthe general procedure D.

LC-MS (m/z): 386 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 1.63 (m, 4H), 1.76(m, 2H), 1.91 (m, 2H), 2.35 (s, 3H), 2.45 (s, 3H), 2.55 (s, 3H), 3.89(m, 1H), 7.42 (d, 1H), 7.88 (s, 1H), 8.20 (s, 1H), 10.80 (br, 1H), 12.25(br, 1H).

Example 3371-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-nitro-thiazol-2-yl)-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-nitro-thiazol-2-yl)-urea(103 mg, 55%) was prepared from(2-amino-5-methyl-phenyl)-cyclopentyl-methanone (102 mg, 0.5 mmol) and5-nitro-thiazol-2-ylamine (87 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 375 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 1.64 (m, 4H), 1.76(m, 2H), 1.91 (m, 2H), 2.36 (s, 3H), 3.91 (m, 1H), 7.44 (d, 1H), 7.91(d, 1H), 8.21 (d, 1H), 8.58 (s, 1H), 10.97 (br, 1H), 12.25 (br, 1H).

Example 3381-(4-tert-Butyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea

1-(4-tert-Butyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea(127 mg, 66%) was prepared from(2-amino-5-methyl-phenyl)-cyclopentyl-methanone (102 mg, 0.5 mmol) and4-tert-butyl-thiazol-2-ylamine (94 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 386 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 1.24 (s, 9H), 1.62(m, 4H), 1.76 (m, 2H), 1.91 (m, 2H), 2.32 (s, 3H), 3.87 (m, 1H), 6.63(s, 1H), 7.37 (d, 1H), 7.83 (d, 1H), 8.13 (d, 1H), 10.53 (br, 1H), 11.82(br, 1H).

Example 3391-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-pyridin-2-yl-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-pyridin-2-yl-urea (94 mg,58%) was prepared from (2-amino-5-methyl-phenyl)-cyclopentyl-methanone(102 mg, 0.5 mmol) and 2-aminopyridine (57 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 324 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 1.63 (m, 4H), 1.76(m, 2H), 1.91 (m, 2H), 2.35 (s, 3H), 3.90 (m, 1H), 6.03 (d, 1H), 7.42(d, 1H), 7.80 (m, 4H), 8.21 (s, 1H), 10.77 (br, 1H), 12.24 (br, 1H).

Example 3401-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-formyl-thiazol-2-yl)-urea

1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-formyl-thiazol-2-yl)-urea(116 mg, 65%) was prepared from(2-amino-5-methyl-phenyl)-cyclopentyl-methanone (102 mg, 0.5 mmol) and2-amino-thiazol-5-carbaldehyde (77 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 358 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.65 (m, 4H), 1.76(m, 2H); 1.90 (m, 2H), 2.35 (s, 3H), 3.89 (m 1H), 7.43 (d, 1H), 7.89 (d,1H), 8.19 (d, 1H), 8.36 (s, 1H), 9.89 (s, 1H), 10.85 (br, 1H), 12.5 (br,1H).

Example 3411-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(hydroxyimino-methyl)-thiazol-2-yl]-urea

To a mixture of 2M aq NaHCO₃ (5 mL) and1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-formyl-thiazol-2-yl)-urea(72 mg, 0.2 mmol) in THF (5 mL) was added hydroxylamine hydrochloride(200 mg) at room temperature with stirring. The resulting mixture washeated at 60° C. for 12 h. The reaction mixture was cooled and extractedwith ethyl acetate. The organic layer was washed (brine), dried (Na₂SO₄)and concentrated to obtain1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(hydroxyimino-methyl)-thiazol-2-yl]-urea(56 mg, 76%) as a mixture of syn and anti-isomers.

LC-MS (m/z): 373 (M+1)⁺.

Example 342{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyleneaminooxy}-aceticacid

To a mixture of 2M aq NaHCO₃ (5 mL) and1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-formyl-thiazol-2-yl)-urea(72 mg, 0.2 mmol) in THF (5 mL) was added hydroxylamine hydrochloride(200 mg) at room temperature with stirring. The resulting mixture washeated at 60° C. for 12 h. The reaction mixture was cooled, acidified topH 6.5 (citric acid) and extracted with ethyl acetate. The organic layerwas washed (brine), dried (Na₂SO₄) and concentrated to obtain{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyleneaminooxy}-aceticacid (56 mg, 76%) as a mixture of syn and anti-isomers.

LC-MS (m/z): 431 (M+1)⁺.

Example 343

({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}amino)-aceticacid methyl ester

({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-amino)-aceticacid methyl ester (38 mg, 45%) was prepared from1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-formyl-thiazol-2-yl)-urea(0.072 g, 0.2 mmol) and glycine methyl ester hydrochloride following thegeneral procedure O.

LC-MS (m/z): 431 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.64 (m, 4H), 1.76(m, 2H), 1.91 (m, 2H), 2.33 (s, 3H), 3.33 (s, 2H), 3.35 (br, 1H), 3.63(s, 3H), 3.83 (s, 2H), 3.91 (m, 1H), 7.14 (s, 1H), 7.38 (d, 1H), 7.83(s, 1H), 8.17 (s, 1H), 10.63 (br, 1H), 11.56 (br, 1H).

Example 3443-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-acrylicacid ethyl ester

3-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-acrylicacid ethyl ester (96 mg, 80%) was prepared from1-(2-cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-formyl-thiazol-2-yl)-urea(100 mg, 0.28 mmol) and (carbethoxymethylene)-triphenylphosphorane (0.12g, 0.34 mmol) following the general procedure X

LC-MS (m/z): 428 (M+1)⁺, ¹H NMR (400 MHz, CDCl₃): δ 1.33 (t, 3H), 1.69(m, 4H), 1.92 (m, 4H), 2.38 (s, 3H), 3.78 (m, 1H), 4.24 (q, 2H), 6.10(d, 1H), 7.25 (d, 1H), 7.38 (d, 1H), 7.46 (m, 2H), 7.99 (s, 1H), 8.46(d, 1H), 10.40 (br, 1H), 11.72 (br, 1H).

Example 3453-(2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl)-propionicacid ethyl ester

3-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-propionicacid ethyl ester was prepared from3-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-acrylicacid ethyl ester via hydrogenation under the conditions described in thegeneral procedure C

LC-MS (m/z): 430 (M+1)⁺.

Example 3461-[2-(2-Methoxy-benzoyl)-5-methyl-phenyl]-3-thiazol-2-yl-urea

(2-Amino-4-methyl-phenyl)-(2-methoxy-phenyl)-methanone (723 g, 30%) wasprepared from 2-amino-4-methyl-benzoic acid (1.51 g, 10 mmol) followingthe general procedure S.1-[2-(2-methoxy-benzoyl)-5-methyl-phenyl]-3-thiazol-2-yl-urea (129 mg,70%) was prepared from(2-amino-4-methyl-phenyl)-(2-methoxy-phenyl)-methanone (121 mg, 0.5mmol) and 2-aminothiazole (0.060 g, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 368 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 2.42 (s, 3H), 3.75(s, 3H), 6.78 (d, 1H), 6.91 (d, 1H), 6.98 (d, 1H), 7.04 (t, 1H), 7.26(t, 1H), 7.33 (d, 1H), 7.46 (m, 1H), 7.64 (d, 1H), 8.46 (s, 1H), 11.02(br, 1H), 11.67 (br, 1H).

Example 3471-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-thiazol-2-yl-urea

(2-Amino-5-methyl-phenyl)-(2-methoxy-phenyl)-methanone (843 g, 35%) wasprepared from 2-amino-5-methyl-benzoic acid (1.51 g, 0.1 mol) followingthe general procedure S.1-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-3-thiazol-2-yl-urea (132 mg,72%) was prepared from(2-amino-5-methyl-phenyl)-(2-methoxy-phenyl)-methanone (121 mg, 0.5mmol) and 2-aminothiazole (0.060 g, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 368 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 2.23 (s, 3H), 3.76(s, 3H), 6.91 (d, 1H), 7.01 (d, 1H), 7.05 (t, 1H), 7.23 (bs, 1H), 7.29(d, 1H), 7.36 (d, 1H), 7.48 (t, 1H), 7.59 (d, 1H), 8.48 (s, 1H), 10.56(br, 1H), 11.45 (br, 1H).

Example 3481-[5-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-3-thiazol-2-yl-urea

(2-Amino-4-fluoro-phenyl)-(2-methoxy-phenyl)-methanone (784 mg, 32%) wasprepared from 2-amino-4-fluoro-benzoic acid (1.55 g, 0.1 mol) followingthe general procedure S.1-[5-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-3-thiazol-2-yl-urea (127 mg,68%) was prepared from(2-amino-4-fluoro-phenyl)-(2-methoxy-phenyl)-methanone (123 mg, 0.5mmol) and 2-aminothiazole (0.060 g, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 372 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 3.75 (s, 3H), 6.66(m, 1H), 6.93 (d, 1H), 6.98 (t, 1H), 7.05 (t, 1H), 7.29 (d, 1H), 7.48(m, 2H), 7.63 (d, 1H), 8.45 (dd, 1H), 11.18 (br, 1H), 11.84 (br, 1H).

Example 3491-[5-Fluoro-2-(thiophene-2-carbonyl)-phenyl]-3-thiazol-2-yl-urea

(2-Amino-4-fluoro-phenyl)-thiophen-2-yl-methanone was (618 g, 28%) wasprepared from 2-amino-4-fluoro-benzoic acid (1.55 g, 10 mmol) followingthe general procedure S.N-[5-Fluoro-2-(thiophene-2-carbonyl)-phenyl]-N′-(thiazol-2-yl)urea (113mg, 65%) was prepared from(2-amino-4-fluoro-phenyl)-thiophen-2-yl-methanone (110 mg, 0.5 mmol) and2-aminothiazole (0.060 g, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 348 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 7.03 (m, 1H), 7.12(d, 1H), 7.27 (t, 1H), 7.35 (d, 1H), 7.64 (d, 1H), 7.80 (dd, 1H), 8.07(d, 1H), 8.14 (d, 1H), 9.63 (br, 1H), 11.60 (br, 1H).

Example 350N-[2-(2-Methoxy-benzoyl)-5-methoxy-phenyl]-N′-(thiazol-2-yl)urea

(2-Amino-4-methoxy-phenyl)-(2-methoxy-phenyl)-methanone (720 mg, 28%)was prepared from 2-amino-4-methoxy-benzoic acid (1.67 g, 0.1 mol)following the general procedure S.N-[2-(2-Methoxy-benzoyl)-5-methoxy-phenyl]-N′-(thiazol-2-yl)urea (131mg, 68%) was prepared from(2-amino-4-methoxy-phenyl)-(2-methoxy-phenyl)-methanone (129 mg, 0.5mmol) and 2-aminothiazole (0.060 g, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 384 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 3.77 (s, 3H), 3.93(s, 3H), 6.91 (d, 1H), 6.98 (d, 1H), 7.04 (t, 1H), 7.23 (d, 1H), 7.25(d, 1H), 7.36 (d, 1H), 7.45 (m, 1H), 7.54 (br, 1H), 8.27 (d, 1H), 10.20(br, 1H), 12.10 (br, 1H).

Example 351(2-{3-[2-(2-Methoxy-benzoyl)-5-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid ethyl ester

(2-{3-[2-(2-Methoxy-benzoyl)-5-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid ethyl ester (163 mg, 72%) was prepared from(2-amino-4-methyl-phenyl)-(2-methoxy-phenyl)-methanone (121 mg, 0.5mmol) and (2-amino-thiazol-4-yl)-acetic acid ethyl ester (111 mg, 0.6mmol) following the general procedure D.

LC-MS (m/z): 454 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.25 (t, 3H), 2.40(s, 3H), 3.69 (s, 2H), 3.72 (s, 3H), 4.20 (q, 2H), 6.71 (s, 1H), 6.76(d, 1H), 6.96 (d, 1H), 7.02 (t, 1H), 7.23 (d, 1H), 7.30 (d, 1H), 7.44(t, 1H), 8.47 (s, 1H), 9.47 (br, 1H), 11.57 (br, 1H).

Example 352(2-{3-[2-(2-Methoxy-benzoyl)-5-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid

(2-{3-[2-(2-Methoxy-benzoyl)-5-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid (181 mg, 85%) was prepared from(2-{3-[2-(2-methoxy-benzoyl)-5-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid ethyl ester (227 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 426 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 2.36 (s, 3H), 3.57(s, 2H), 3.68 (s, 3H), 6.86 (s, 1H), 7.07 (t, 1H), 7.22 (m, 2H), 7.31(d, 1H), 7.50 (t, 2H), 8.26 (s, 1H), 10.92 (br, 1H), 12.20 (br, 1H).

Example 3532-(2-{3-[2-(2-Methoxy-benzoyl)-5-methyl-phenyl]-ureido}-thiazol-4-yl)-N-methyl-acetamide

2-(2-{3-[2-(2-Methoxy-benzoyl)-5-methyl-phenyl]-ureido}-thiazol-4-yl)-N-methyl-acetamide(164 mg, 75%) was prepared from(2-{3-[2-(2-methoxy-benzoyl)-5-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid (213 mg, 0.5 mmol) and 1 N solution of methylamine in THF (0.5 mL,0.5 mmol) following the general procedure K.

LC-MS (m/z): 439 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 2.41 (s, 3H), 2.74(d, 3H), 3.62 (s, 2H), 3.73 (s, 3H), 6.66 (s, 1H), 6.79 (d, 1H), 6.97(d, 1H), 7.03 (t, 1H), 7.24 (d, 1H), 7.32 (d, 1H), 7.46 (m, 1H), 8.45(s, 1H), 11.60 (br, 1H), 11.82 (br, 1H).

Example 3542-(2-{3-[2-(2-Methoxy-benzoyl)-5-methyl-phenyl]-ureido}-thiazol-4-yl)-N-(methoxy-ethyl)-acetamide

2-(2-{3-[2-(2-Methoxy-benzoyl)-5-methyl-phenyl]-ureido}-thiazol-4-yl)-N-(methoxy-ethyl)-acetamide(169 mg, 70%) was prepared from(2-{3-[2-(2-methoxy-benzoyl)-5-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid (213 mg, 0.5 mmol) and 2-methoxyethylamine (38 mg, 0.5 mmol)following the general procedure K.

LC-MS (m/z): 483 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 2.41 (s, 3H), 3.33(s, 3H), 3.48 (m, 4H), 3.61 (s, 2H), 3.73 (s, 3H), 6.65 (s, 1H), 6.76(d, 1H), 6.97 (d, 1H), 7.03 (t, 1H), 7.25 (d, 1H), 7.31 (d, 1H), 7.42(bs, 1H), 7.46 (m, 1H), 8.48 (s, 1H), 10.02 (br, 1H), 11.62 (br, 1H).

Example 355N-(2-Methanesulfonyl-ethyl)-2-(2-{3-[2-(2-methoxy-benzoyl)-5-methyl-phenyl]-ureido}-thiazol-4-yl)-acetamide

N-(2-Methanesulfonyl-ethyl)-2-(2-{3-[2-(2-methoxy-benzoyl)-5-methyl-phenyl]-ureido}-thiazol-4-yl)-acetamide(181 mg, 68%) was prepared from(2-{3-[2-(2-methoxy-benzoyl)-5-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid (213 mg, 0.5 mmol) and 2-methanesulfonyl-ethylamine (61 mg, 0.5mmol) following the general procedure K.

LC-MS (m/z): 531 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 2.41 (s, 3H), 2.93(s, 3H), 3.33 (t, 3H), 3.63 (s, 2H), 3.74 (s, 3H), 3.78 (m, 2H), 6.61(s, 1H), 6.76 (d, 1H), 6.98 (d, 1H), 7.04 (t, 1H), 7.25 (d, 1H), 7.31(d, 1H), 7.46 (m, 1H), 7.97 (t, 1H), 8.48 (s, 1H), 11.40 (br, 1H), 11.51(br, 1H).

Example 356(2-{3-[5-Fluoro-2-(2-Methoxy-benzoyl)-phenyl]-ureido}-thiazol-4-yl)-aceticacid ethyl ester

(2-{3-[5-Fluoro-2-(2-Methoxy-benzoyl)-phenyl]-ureido}-thiazol-4-yl)-aceticacid ethyl ester (164 mg, 72%) was prepared from(2-amino-4-fluoro-phenyl)-(2-methoxy-phenyl)-methanone (123 mg, 0.5mmol) and (2-amino-thiazol-4-yl)-acetic acid ethyl ester (111 mg, 0.6mmol) following the general procedure (D).

LC-MS (m/z): 458 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.24 (t, 3H), 3.68(s, 2H), 3.78 (s, 3H), 6.68 (s, 1H), 6.74 (d, 1H), 6.93 (d, 1H), 7.06(t, 1H), 7.24 (m, 1H), 7.30 (d, 1H), 7.44 (t, 1H), 8.47 (s, 1H), 9.47(br, 1H), 11.57 (br, 1H).

Example 357(2-{3-[5-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-ureido}-thiazol-4-yl)-aceticacid

(2-{3-[5-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-ureido}-thiazol-4-yl)-aceticacid (161 mg, 75%) was prepared from(2-{3-[5-fluoro-2-(2-methoxy-benzoyl)-phenyl]-ureido}-thiazol-4-yl)-aceticacid ethyl ester (229, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 430 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 3.57 (s, 2H), 3.69(s, 3H), 6.89 (m, 2H), 7.08 (t, 1H), 7.18 (d, 1H), 7.33 (d, 1H), 7.40(m, 1H), 7.54 (m, 1H), 8.28 (d, 1H), 11.12 (br, 1H), 12.32 (br, 1H).

Example 3582-(2-{3-[5-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-ureido}-thiazol-4-yl)-N-methyl-acetamide

2-(2-{3-[5-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-ureido}-thiazol-4-yl)-N-methyl-acetamide(144 mg, 65%) was prepared from(2-{3-[5-fluoro-2-(2-methoxy-benzoyl)-phenyl]-ureido}-thiazol-4-yl)-aceticacid (215 mg, 0.5 mmol) and 1N solution of methyl amine in THF (0.5 mL,0.5 mmol) following the general procedure K.

LC-MS (m/z): 443 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 2.71 (d, 3H), 3.66(s, 2H), 3.70 (s, s, 3H), 6.64 m, 2H), 6.85 (br, 1H), 7.36 (m, 2H), 6.95(d, 1H), 7.02 (t, 1H), 7.24 (dd, 1H), 7.44 (m, 2H), 8.43 (dd, 1H), 10.72(br, 1H), 11.84 (br, 1H).

Example 3592-(2-{3-[5-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-ureido}-thiazol-4-yl)-N-(2-methoxy-ethyl)-acetamide

2-(2-{3-[5-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-ureido}-thiazol-4-yl)-N-(2-methoxy-ethyl)-acetamide(158 mg, 65%) was prepared from(2-{3-[5-fluoro-2-(2-methoxy-benzoyl)-phenyl]-ureido}-thiazol-4-yl)-aceticacid (215 mg, 0.5 mmol) and 2-methoxylethylamine (38 mg, 0.5 mmol)following the general procedure K.

LC-MS (m/z): 487 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 3.21 (s, 3H), 3.48(m, 4H), 3.62 (s, 2H), 3.73 (s, 3H), 6.62-6.66 (m, 2H), 6.97 (d, 1H),7.04 (t, 1H), 7.28 (d, 1H), 7.42 (br, 1H), 7.42-7.50 (m, 2H), 8.46 (dd,1H), 10.20 (br, 1H), 11.28 (br, 1H),

Example 3601-[2-(Hydroxyimino-phenyl-methyl)-phenyl]-3-thiazol-2-yl-urea

1-[2-(Hydroxyimino-phenyl-methyl)-phenyl]-3-thiazol-2-yl-urea (101 mg,60%) was prepared from (2-Amino-phenyl)-phenyl-methanone oxime (106 mg,0.5 mmol) and 2-amino thiazole (0.06 mg, 0.6 mmol) following the generalprocedure D.

LC-MS (m/z): 339 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 7.2 (dd, 1H), 7.06(d, 1H), 7.15 (m, 1H), 7.30 (d, 1H), 7.34-7.43 (m, 6H), 8.03 (d, 1H),8.05 (br, 1H), 11.07 (br, 1H), 11.63 (br, 1H),

Example 3611-[5-Chloro-2-(hydroxyimino-phenyl-methyl)-phenyl]-3-thiazol-2-yl-urea

1-[5-Chloro-2-(hydroxyimino-phenyl-methyl)-phenyl]-3-thiazol-2-yl-urea(93 mg, 50%) was prepared from(2-Amino-4-chloro-phenyl)-phenyl-methanone oxime (123 mg, 0.5 mmol) and2-amino thiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 373 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 7.04 (dd, 1H),7.12 (d, 1H), 7.16 (m, 1H), 7.36 (d, 1H), 7.36-7.48 (m, 5H), 8.03 (d,1H), 8.12 (br, 1H), 11.23 (br, 1H), 11.72 (br, 1H),

Example 362 1-(2-Benzoyl-5-methyl-phenyl)-3-thiazol-2-yl-urea

1-(2-Benzoyl-5-methyl-phenyl)-3-thiazol-2-yl-urea (60 mg, 65%) wasprepared from (2-(2-amino-4-methyl-phenyl)-phenyl-methanone (55 mg, 0.25mmol) following the general procedure D.

LC-MS (m/z): 338 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 2.40 (s, 3H), 6.93(s, 1H), 7.19 (t, 1H), 7.28 (s, 1H), 7.48 (t, 1H), 7.54-7.61 (m, 4H),7.68 (dd, 1H), 8.54 (d, 1H), 10.64 (br, 1H), 11.22 (br, 1H).

Example 363 1-[4-Bromo-2-(2-fluoro-benzoyl)-phenyl]-3-thiazol-2-yl-urea

1-[4-Bromo-2-(2-fluoro-benzoyl)-phenyl]-3-thiazol-2-yl-urea (73 mg, 69%)was prepared from (2-amino-5-bromo-phenyl)-(2-fluoro-phenyl)-methanone(73 mg, 0.25 mmol) following the general procedure D.

LC-MS (m/z): 420 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 6.93 (s, 1H), 7.19(t, 1H), 7.28 (s, 1H), 7.48 (t, 1H), 7.54-7.61 (m, 3H), 7.68 (dd, 1H),8.54 (d, 1H), 10.64 (br, 1H), 11.22 (br, 1H).

Example 364 1-[5-Chloro-2-(2-fluoro-benzoyl)-phenyl]-3-thiazol-2-yl-urea

1-[5-Chloro-2-(2-fluoro-benzoyl)-phenyl]-3-thiazol-2-yl-urea (132 mg,70%) was prepared from(2-amino-4-chloro-phenyl)-(2-fluoro-phenyl)-methanone (125 mg, 0.5 mmol)and 2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 376 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 6.76 (s, 1H), 6.89(s, 1H), 7.16 (m, 1H), 7.25 (d, 1H), 7.48 (m, 4H), 8.58 (br, 1H), 10.88(br, 1H).

Example 3651-[4-Fluoro-2-(2-methylsulfanyl-phenoxy)-phenyl]-3-thiazol-2-yl-urea

4-Fluoro-2-(2-methylsulfanylphenoxy)-1-nitrobenzene (1.06 g, 68%) wasprepared from 2-hydroxythioanisole (0.77 g, 5.5 mmol) and2,5-difluoro-1-nitro-benzene (0.80 g, 5.0 mmol) following the generalprocedure A. This was reduced to4-fluoro-2-(2-methanesulfanyl-phenoxy)-phenylamine (0.52 g, 62%)following general procedure C.1-[4-Fluoro-2-(2-methylsulfanyl-phenoxy)-phenyl]-3-thiazol-2-yl-urea(117 mg, 60%) was prepared from4-fluoro-2-(2-methylsulfanylphenoxy)aniline (125 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 376 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 2.41 (s, 3H), 6.41(dd, 1H), 6.56 (br, 1H), 6.76 (d, 1H), 6.94 (d, 1H), 7.15-7.34 (m, 4H),8.26 (dd, 1H), 9.88 (br, 1H), 11.12 (br, 1H),

Example 3662-[4-Fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-6-methoxy-benzoic acidmethyl ester

2-(4-Fluoro-2-nitro-phenoxy)-6-methoxy-benzoic acid methyl ester (0.94g, 58%) was prepared from 2-hydroxy-6-methoxy-benzoic acid methyl ester(1.01 g, 5.5 mmol) and 2,5-difluoro-1-nitro-benzene (0.80 g, 5.0 mmol)following the general procedure A. This was reduced to2-(2-amino-4-fluoro-phenoxy)-6-methoxy-benzoic acid methyl ester (0.51g, 60%) following general procedure C.2-[4-Fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-6-methoxy-benzoic acidmethyl ester (129 mg, 62%) was prepared from2-(2-amino-4-fluoro-phenoxy)-6-methoxy-benzoic acid methyl ester (145mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 418 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 3.62 (s, 3H), 3.64(s, 3H), 6.31 (s, 1H), 6.45 (dd, 1H), 6.55 (s, 1H), 7.05 (d, 1H), 7.22(t, 1H), 7.33 (br, 1H), 7.45 (d, 1H), 78.02 (d, 1H), 8.63 (br, 1H),11.74 (br, 1H).

Example 3672-[4-Fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-6-methoxy-N-methyl-benzamide

2-[4-Fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-6-methoxy-N-methyl-benzamide(150 mg, 72%) was prepared from2-[4-fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-6-methoxy-benzoic acid(201 mg, 0.5 mmol) and 1N solution of methyl amine in THF (0.5 mL, 0.5mmol) following the general procedure K.

LC-MS (m/z): 417 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 3.42 (d, 3H), 3.67(s, 3H), 6.51 (dd, 1H), 6.67 (m, 1H), 7.14 (m, 2H), 7.29 (m, 2H), 7.37(d, 1H), 7.98 (dd, 1H), 8.11 (d, 1H), 9.13 (dd, 1H), 11.20 (br, 1H).

Example 3681-[5-Fluoro-2-(2-methanesulfonyl-phenoxy)-phenyl]-3-thiazol-2-yl-urea

1-[5-Fluoro-2-(2-methanesulfonyl-phenoxy)-phenyl]-3-thiazol-2-yl-urea(153 mg, 75%) was prepared from1-[5-fluoro-2-(2-methanesulfanyl-phenoxy)-phenyl]-3-thiazol-2-yl-urea(187 mg, 0.5 mmol) following the general procedure R.

LC-MS (m/z): 408 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 3.44 (s, 3H), 6.80(m, 1H), 6.84 (d, 1H), 7.03 (d, 1H), 7.27 (m, 2H), 7.33 (d, 1H), 7.56(m, 1H), 8.05 (dd, 1H), 8.27 (dd, 1H), 9.13 (br, 1H), 11.12 (br, 1H).

Example 3691-[2-(4,5-Dimethoxy-2-methyl-phenoxy)-phenyl]-3-thiazol-2-yl-urea

1-[2-(4,5-Dimethoxy-2-methyl-phenoxy)-phenyl]-3-thiazol-2-yl-urea (131mg, 68%) was prepared from2-(4,5-dimethoxy-2-methyl-phenoxy)-phenylamine (130 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LC-MS (m/z): 386 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 2.29 (s, 3H), 3.80(s, 3H), 3.94 (s, 3H), 6.76 (s, 1H), 6.92 (d, 1H), 7.02 (t, 1H), 7.44(d, 1H), 7.55 (t, 2H), 7.76 (d, 1H), 8.54 (d, 1H), 11.34 (br, 1H).

Example 370 3-[4-Fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-benzoic acidmethyl ester

3-(4-Fluoro-2-nitro-phenoxy)-benzoic acid methyl ester (0.73 g, 50%) wasprepared from 3-hydroxy-benzoic acid methyl ester (0.84 g, 5.5 mmol) and2,5-difluoro-1-nitro-benzene (0.80 g, 5.0 mmol) following the generalprocedure A. This was reduced to 2-(2-amino-4-fluoro-phenoxy)-benzoicacid methyl ester (0.37 g, 58%) following general procedure C.3-[4-Fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-benzoic acid methyl ester(145 mg, 75%) was prepared from 3-(2-amino-4-fluoro-phenoxy)-benzoicacid methyl ester (130 mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6mmol) following the general procedure D.

LC-MS (m/z): 388 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 3.87 (s, 3H), 6.78(m, 1H), 6.89 (d, 1H), 7.12 (m, 1H), 7.18 (br, 1H), 7.34 (m, 1H), 7.41(m, 1H), 7.60 (m, 1H), 7.72 (d, 1H), 8.22 (dd, 1H), 10.50 (br, 1H).

Example 371 3-[4-Fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-benzoic acid

3-[4-Fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-benzoic acid (150 mg,80%) was prepared from3-[4-fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-benzoic acid methyl ester(194 mg, 0.5 mmol) following the general procedure J

LC-MS (m/z): 374 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 6.85 (m, 1H), 7.01(dd, 1H), 7.13 (d, 1H), 7.26 (dd, 1H), 7.34 (d, 1H), 7.42 (m, 1H), 7.52(t, 1H), 8.14 (dd, 1H), 9.47 (br, 1H), 11.28, br, 1H).

Example 372 2-[4-Fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-benzoic acidmethyl ester

2-(4-Fluoro-2-nitro-phenoxy)-benzoic acid methyl ester (0.81 g, 55%) wasprepared from 2-hydroxy-benzoic acid methyl ester (0.84 g, 5.5 mmol) and2,5-difluoro-1-nitro-benzene (0.80 g, 5.0 mmol) following the generalprocedure A. This was reduced to 2-(2-amino-4-fluoro-phenoxy)-benzoicacid methyl ester (0.43 g, 60%) following general procedure C.2-[4-Fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-benzoic acid methyl ester(125 mg, 65%) was prepared from 2-(2-amino-4-fluoro-phenoxy)-benzoicacid methyl ester (130 mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6mmol) following the general procedure D.

LC-MS (m/z): 388 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 3.84 (s, 3H), 6.73(m, 1H), 6.85 (d, 1H), 7.14 (m, 1H), 7.13 (br, 1H), 7.31 (m, 1H), 7.41(m, 1H), 7.54 (m, 1H), 7.71 (d, 1H), 8.22 (dd, 1H), 10.54 (br, 1H).

Example 3732-[4-Fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-N-methyl-benzamide

2-[4-Fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-N-methyl-benzamide wasprepared from 2-[4-fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-benzoicacid and 1N solution of methyl amine in THF (0.5 mL, 0.5 mmol) followingthe general procedure K.

LC-MS (m/z): 387 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 3.53 (d, 3H), 6.73(m, 1H), 5.86 (br, 1H), 6.88 (d, 1H), 7.16 (m, 1H), 7.18 (br, 1H), 7.35(m, 1H), 7.41 (m, 1H), 7.60 (m, 1H), 7.76 (d, 1H), 8.23 (dd, 1H), 10.22(br, 1H).

Example 374N-{3-[4-Fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-2-methoxy-phenyl}-methanesulfonamide

N-[3-(4-Fluoro-2-nitro-phenoxy)-2-methoxy-phenyl]-methanesulfonamide(0.86 g, 48%) was prepared fromN-(3-hydroxy-2-methoxy-phenyl)-methanesulfonamide (1.2 g, 5.5 mmol) and2,5-difluoro-1-nitro-benzene (0.80 g, 5.0 mmol) following the generalprocedure A. This was reduced toN-[3-(2-amino-4-fluoro-phenoxy)-2-methoxy-phenyl]-methanesulfonamide(0.51 g, 70%) following general procedure C.N-{3-[4-Fluoro-2-(3-thiazol-2-yl-ureido)-phenoxy]-2-methoxy-phenyl}-methanesulfonamide(144 mg, 64%) was prepared fromN-[3-(2-amino-4-fluoro-phenoxy)-2-methoxy-phenyl]-methanesulfonamide(123 mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LC-MS (m/z): 453 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 3.27 (s, 3H), 3.89(s, 3H), 6.52 (d, 1H), 6.72 (m, 1H), 6.95 (d, 1H), 7.04 (m, 1H), 7.16(m, 1H), 7.34 (d, 1H), 7.45 (dd, 1H), 7.63 (d, 1H), 8.21 (dd, 1H), 8.44(br, 1H), 8.85 (br, 1H).

Example 375N-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-acetamide

N-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-acetamide(81 mg, 78%) was prepared fromN-[3-amino-4-(2-fluoro-6-methoxy-phenoxy)-phenyl]-acetamide (72 mg, 0.25mmol) following the general procedure D.

LC-MS (m/z): 417 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.78 (s, 3H), 3.43(s, 3H), 6.32 (m, 1H), 6.44 (dd, 1H), 6.48 (d, 1H), 6.63 (t, 1H), 6.86(dd, 1H), 6.97 (d, 1H), 7.13 (d, 1H), 7.88 (d, 1H), 8.90 (br, 1H), 9.32(br, 1H), and 10.46 (br, 1H).

Example 376N-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-methanesulfonamide

N-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]methanesulfonamide(101 mg, 89%) was prepared fromN-[3-amino-4-(2-fluoro-6-methoxy-phenoxy)-phenyl]-methanesulfonamide (81mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 453 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 3.13 (s, 3H), 4.00(s, 3H), 6.70 (d, 1H), 6.98 (dd, 1H), 7.14 (t, 1H), 7.21 (d, 1H), 7.38(t, 1H), 7.46 (q, 1H), 7.55 (t, 1H), 8.14 (br, 1H), 8.38 (dd, 1H), 8.46(d, 1H), and 10.86 (br, 1H).

Example 377(2-{3-[2-(2-Fluoro-6-methoxy-phenoxy)-5-methanesulfonylamino-phenyl]-ureido}-thiazol-4yl)-acetic acid ethyl ester

(2-{3-[2-(2-Fluoro-6-methoxy-phenoxy)-5-methanesulfonylamino-phenyl]-ureido}-thiazol-4yl)-acetic acid ethyl ester (118 mg, 87%) was prepared fromN-[3-amino-4-(2-fluoro-6-methoxy-phenoxy)-phenyl]-methanesulfonamide (81mg, 0.25 mmol) following the general procedure D.

LC-MS (m/z): 539 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.24 (t, 2H), 3.03(s, 3H), 3.74 (s, 2H), 3.80 (s, 3H), 4.21 (q, 3H), 6.59 (d, 1H), 6.68(s, 1H), 6.78 (s, 1H), 6.83 (dd, 1H), 7.12-7.19 (m, 2H), 8.12 (d, 1H),8.42 (s, 1H), 9.60 (br, 1H), and 11.84 (br, 1H).

Example 378(2-{3-[2-(2-Fluoro-6-methoxy-phenoxy)-5-methanesulfonylamino-phenyl]-ureido}-thiazol-4-yl)-aceticacid

(2-{3-[2-(2-Fluoro-6-methoxy-phenoxy)-5-methanesulfonylamino-phenyl]-ureido}-thiazol-4-yl)-aceticacid (85 mg, 83%) was prepared from(2-{3-[2-(2-fluoro-6-methoxy-phenoxy)-5-methanesulfonylamino-phenyl]-ureido}-thiazol-4yl)-acetic acid ethyl ester (108 mg, 0.20 mmol) following the generalprocedure J.

LC-MS (m/z): 511 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 3.12 (s, 3H), 3.54(s, 2H), 3.81 (s, 3H), 6.54 (d, 1H), 6.64 (s, 1H), 6.84 (s, 1H), 6.92(d, 1H), 7.11 (m, 1H), 7.16 (s, 1H), 7.44 (m, 1H), 8.46 (s, 1H), 9.40(br, 1H), 10.83 (br, 1H), and 11.84 (br, 1H).

Example 379N,N-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]dimethanesulfonamide

N,N-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]dimethanesulfonamide(115 mg, 87%) was prepared fromN-[3-amino-4-(2-fluoro-6-methoxy-phenoxy)-phenyl]-dimethanesulfonamide(101 mg, 0.25 mmol) following the general procedure D.

LC-MS (m/z): 531 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 3.22 (s, 3H), 3.24(s, 3H), 4.11 (s, 3H), 6.78 (d, 1H), 6.89 (d, 1H), 7.11 (dd, 1H), 7.24(d, 1H), 7.29 (m, 1H), 7.42 (t, 1H), 7.63 (m, 1H), 8.54 (d, 1H), 8.65(dd, 1H), and 11.38 (br, 1H).

Example 380N-[4-Isobutoxy-3-(3-thiazol-2-yl-ureido)-phenyl]-methanesulfonamide

N-[4-Isobutoxy-3-(3-thiazol-2-yl-ureido)-phenyl]-methanesulfonamide (77mg, 80%) was prepared fromN-(3-amino-4-isobutoxy-phenyl)-methanesulfonamide (64 mg, 0.25 mmol)following the general procedure D.

LC-MS (m/z): 385 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.20 (d, 6H), 1.70(m, 1H), 3.05 (d, 2H), 3.82 (s, 3H), 6.76 (dd, 1H), 6.86 (d, 1H), 6.94(m, 1H), 7.36 (d, 1H), 7.42 (d, 1H), 8.42 (d, 1H), 9.56 (br, 1H), and11.63 (br, 1H).

Example 3811-[5-Amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea

1-[5-Amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(3.52 g, 94%) was prepared from3-amino-4-(2-fluoro-6-methoxy-phenoxy)-phenyl]-carbamic acid tert-butylester (3.48 g, 10.0 mmol) following the general procedure D and thecorresponding t-BOC protected product[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-carbamicacid tert-butyl ester was subjected to deprotection conditions withhydrochloric acid (40 ml, 4.0 M in dioxane).

LC-MS (m/z): 375 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 3.76 (s, 3H), 5.24(br, 2H), 6.68 (d, 1H), 6.88 (q, 1H), 6.98 (d, 1H), 7.16 (m, 1H), 7.38(dd, 1H), 7.63 (dd, 1H), 8.34 (dd, 1H), 8.44 (d, 1H), 8.86 (br, 1H), and11.27 (br, 1H).

Example 382 Pyridine-2-carboxylic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide

Pyridine-2-carboxylic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide(98 mg, 82%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure K.

LC-MS (m/z): 480 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 3.74 (s, 3H), 6.64(d, 1H), 6.74 (d, 1H), 6.78 (s, 1H), 6.82 (m, 1H), 7.16 (q, 1H), 7.46(dd, 1H), 7.48 (d, 1H), 7.54 (t, 1H), 7.72 (br, 1H), 7.84 (dd, 1H), 7.88(t, 1H), 8.24 (d, 1H), 8.38 (br, 1H), 8.62 (d, 1H), and 10.06 (br, 1H).

Example 383N-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-isonicotinamide

N-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-isonicotinamide(104 mg, 86%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure K.

LC-MS (m/z): 480 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 3.58 (s, 3H), 6.32(d, 1H), 6.62 (dd, 1H), 6.64 (d, 1H), 6.66 (d, 1H), 6.96 (m, 2H), 7.06(d, 1H), 7.18 (dd, 1H), 7.60 (d, 2H), 8.12 (d, 1H), 8.40 (br, 1H), 8.48(d, 1H), 9.62 (d, 1H), and 11.34 (br, 1H).

Example 384 5-Methyl-pyrazine-2-carboxylic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide

5-Methyl-pyrazine-2-carboxylic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide(103 mg, 83%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure K.

LC-MS (m/z): 495 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 2.68 (s, 3H), 3.63(s, 3H), 6.52 (d, 1H), 6.61 (d, 1H), 6.66 (d, 2H), 7.06 (q, 1H), 7.36(s, 1H), 7.78 (d, 1H), 8.20 (br, 1H), 8.43 (s, 1H), 8.76 (br, 1H), 9.32(s, 1H), 9.62 (s, 1H), and 11.80 (br, 1H).

Example 385 2,2,2-Trifluoro-ethanesulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide

2,2,2-Trifluoro-ethanesulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide(105 mg, 81%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 521 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 3.75 (s, 3H), 3.86(q, 2H), 6.48 (d, 1H), 6.80 (m, 2H), 6.88 (d, 1H), 7.16 (q, 1H), 7.28(d, 1H), 7.47 (s, 1H), 8.08 (d, 1H), 8.40 (br, 1H), 9.62 (d, 1H), and11.34 (br, 1H).

Example 386N-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-C-methanesulfonyl-methanesulfonamide

N-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-C-methanesulfonyl-methanesulfonamide(102 mg, 77%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 530 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 3.01 (s, 3H), 3.27(s, 2H), 3.82 (s, 3H), 6.56 (d, 1H), 6.85 (t, 1H), 6.94 (d, 1H), 7.21(q, 1H), 7.34 (d, 1H), 7.46 (m, 1H), 7.96 (s, 1H), 8.22 (d, 1H), 8.40(br, 1H), 9.62 (br, 1H), and 10.94 (br, 1H).

Example 387 1-Methyl-1H-imidazole-4-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide

1-Methyl-1H-imidazole-4-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide(108 mg, 83%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 519 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 3.00 (s, 3H), 3.78(s, 3H), 6.46 (d, 1H), 6.74 (dd, 1H), 6.83 (d, 2H), 6.91 (d, 1H),7.16-7.22 (m, 1H), 7.31 (d, 1H), 7.48 (m, 1H), 7.66 (s, 1H), 7.99 (d,1H), 8.18 (d, 1H), 9.88 (br, 1H), and 11.24 (br, 1H).

Example 388 1,2-Dimethyl-1H-imidazole-4-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide

1,2-Dimethyl-1H-imidazole-4-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide(115 mg, 86%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 533 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 2.74 (s, 3H), 3.20(s, 3H), 3.99 (s, 3H), 6.79 (d, 1H), 7.09 (dd, 1H), 7.34 (t, 1H), 7.44(d, 1H), 7.48 (d, 1H), 7.67 (q, 1H), 7.78 (d, 1H), 8.01 (s, 1H), 8.36(s, 1H), 8.46 (d, 1H), 9.88 (br, 1H), and 11.24 (br, 1H).

Example 3891-[2-(2-Fluoro-6-methoxy-phenoxy)-5-methylamino-phenyl]-3-thiazol-2-yl-urea

1-[2-(2-Fluoro-6-methoxy-phenoxy)-5-methylamino-phenyl]-3-thiazol-2-yl-urea(85 mg, 88%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure O.

LC-MS (m/z): 389 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 3.66 (s, 3H), 4.09(s, 3H), 5.62 (br, 1H), 6.82 (d, 1H), 6.99 (s, 1H), 7.16 (m, 1H), 7.40(d, 1H), 7.45-7.53 (m, 1H), 7.58 (d, 1H), 7.64 (d, 1H), 8.76 (d, 1H),9.38 (br, 1H), and 11.27 (br, 1H).

Example 3901-[2-(2-Fluoro-6-methoxy-phenoxy)-5-(1-methyl-3-thiazol-2-yl-ureido)-phenyl]-3-thiazol-2-yl-urea

1-[2-(2-Fluoro-6-methoxy-phenoxy)-5-(1-methyl-3-thiazol-2-yl-ureido)-phenyl]-3-thiazol-2-yl-urea(86 mg, 67%) was prepared from4-(2-fluoro-6-methoxy-phenoxy)-N′1′-methyl-benzene-1,3-diamine (64 mg,0.25 mmol) following the general procedure D.

LC-MS (m/z): 515 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 3.32 (s, 3H), 3.73(s, 3H), 5.40 (br, 1H), 6.46 (d, 2H), 6.54 (d, 1H), 6.74 (d, 1H), 6.80(d, 1H), 7.08 (d, 2H), 7.22 (d, 1H), 7.33 (br, 1H), 8.38 (d, 1H), 9.03(br, 1H), and 11.27 (br, 1H).

Example 3911-[5-Dimethylamino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea

1-[5-Dimethylamino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(85 mg, 85%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure O.

LC-MS (m/z): 403 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 2.93 (s, 6H), 3.66(s, 3H), 6.38 (d, 1H), 6.49 (t, 1H), 6.62-6.74 (m, 2H), 7.07 (t, 1H),7.39 (d, 1H), 7.84 (s, 1H), 8.00 (br, 1H), 8.42 (br, 1H), and 11.52 (br,1H).

Example 3921-{2-(2-Fluoro-6-methoxy-phenoxy)-5-[(pyridin-3-ylmethyl)-amino]-phenyl}-3-thiazol-2-yl-urea

1-{2-(2-Fluoro-6-methoxy-phenoxy)-5-[(pyridin-3-ylmethyl)-amino]-phenyl}-3-thiazol-2-yl-urea(98 mg, 84%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure O.

LC-MS (m/z): 466 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 3.16 (s, 2H), 3.62(s, 3H), 6.42 (d, 1H), 6.68 (t, 1H), 6.78 (d, 1H), 6.88 (m, 1H), 7.05(q, 1H), 7.21 (s, 1H), 7.41 (m, 1H), 7.52 (m, 1H), 7.81 (br, 1H), 8.00(br, 1H), 8.16 (d, 1H), 8.42 (d, 1H), 8.56 (d, 1H), 8.70 (m, 1H), and11.38 (br, 1H).

Example 3931-[5-(Di-pyridin-2-yl-amino)-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea

1-[5-(Di-pyridin-2-yl-amino)-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(111 mg, 84%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure O.

LC-MS (m/z): 529 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 3.67 (s, 3H), 6.42(d, 1H), 6.46 (d, 1H), 6.50 (d, 2H), 6.72 (q, 2H), 6.87 (m, 4H),7.02-7.10 (m, 2H), 7.42 (m, 1H), 7.54 (m, 1H), 8.14 (d, 2H), 9.70 (br,1H), and 11.58 (br, 1H).

Example 394 Propane-1-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide

Propane-1-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide(100 mg, 83%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 481 (M+1)⁺; ¹H NMR (400 MHz, Acetone-d₆): δ 1.02 (t, 3H),1.84 (m, 2H), 3.08 (t, 2H), 3.82 (s, 3H), 6.56 (d, 1H), 6.88 (d, 1H),6.96-7.00 (m, 1H), 7.24 (q, 1H), 7.34 (dd, 1H), 7.88 (s, 1H), 7.99 (br,1H), 8.32 (d, 1H), 8.48 (d, 1H), 8.64 (br, 1H), and 11.12 (br, 1H).

Example 395N-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-C-phenylmethanesulfonamide

N-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-C-phenylmethanesulfonamide (104 mg, 79%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 529 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 3.36 (s, 2H), 3.83(s, 3H), 6.54 (d, 1H), 6.86 (m, 2H), 6.94 (m, 2H), 7.22 (q, 1H), 7.38(m, 5H), 7.42 (d, 1H), 7.96 (br, 1H), 8.06 (d, 1H), 9.34 (br, 1H), and11.24 (br, 1H).

Example 396N-{4-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenylsulfamoyl]-phenyl}-acetamide

N-{4-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenylsulfamoyl]-phenyl}-acetamide(113 mg, 79%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 572 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 3.02 (s, 3H), 3.85(s, 3H), 6.48 (d, 1H), 6.86 (m, 2H), 6.98 (br, 1H), 7.03 (m, 2H), 7.41(m, 3H), 7.76 (m, 3H), 8.23 (d, 1H), 9.06 (br, 1H), 9.54 (br, 1H), and11.24 (br, 1H).

Example 3971-{2-(2-Fluoro-6-methoxy-phenoxy)-5-[(5-methyl-3H-imidazol-4-ylmethyl)-amino]-phenyl}-3-thiazol-2-yl-urea

1-{2-(2-Fluoro-6-methoxy-phenoxy)-5-[(5-methyl-3H-imidazol-4-ylmethyl)-amino]-phenyl}-3-thiazol-2-yl-urea(98 mg, 84%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure O.

LC-MS (m/z): 469 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 2.29 (s, 3H), 2.55(s, 2H), 3.68 (s, 3H), 6.46 (d, 1H), 6.86 (m, 2H), 6.96 (br, 1H), 7.08(d, 1H), 7.41 (m, 1H), 7.49 (m, 2H), 7.54 s, 1H), 7.64 (s, 1H), 7.72 (d,1H), 9.46 (br, 1H), and 11.44 (br, 1H).

Example 3984-Acetyl-N-[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-benzenesulfonamide

4-Acetyl-N-[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-benzenesulfonamide(98 mg, 84%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 557 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 2.61 (s, 3H), 3.78(s, 3H), 6.48 (d, 1H), 6.88 (m, 2H), 7.06 (m, 2H), 7.08 (d, 1H), 7.22(br, 1H), 7.36 (d, 1H), 7.82 (m, 1H), 7.92 (d, 2H), 7.98 (t, 1H), 8.12(d, 1H), 8.24 (br, 1H), and 11.88 (br, 1H).

Example 3994-Cyano-N-[4-(2-fluoro-6-methoxyphenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]benzenesulfonamide

4-Cyano-N-[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]benzenesulfonamide(115 mg, 85%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 540 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 3.76 (s, 3H), 6.52(d, 1H), 6.80 (m, 1H), 6.88 (d, 1H), 7.08 (d, 2H), 7.12-7.18 (m, 1H),7.30 (d, 1H), 7.38 (d, 1H), 7.54 (d, 1H), 7.71 (t, 1H), 7.91 (q, 1H),8.01 (s, 1H), 8.08 (br, 1H), 8.22 (d, 1H), and 11.22 (br, 1H).

Example 400N-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-4-isopropyl-benzenesulfonamide

N-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-4-isopropyl-benzenesulfonamide(103 mg, 74%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 557 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 1.22 (d, 6H), 1.56(m, 1H), 3.74 (s, 3H), 6.54 (d, 1H), 6.78 (m, 2H), 6.84 (d, 1H), 6.98(m, 1H), 7.06 (d, 1H), 7.12-7.18 (m, 2H), 7.22 (d, 1H), 7.34 (d, 1H),7.72 (d, 1H), 8.00 (br, 1H), 8.22 (d, 1H), 8.58 (br, 1H), and 10.74 (br,1H).

Example 401N-{5-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide

N-{5-[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide(121 mg, 82%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 593 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 2.32 (s, 3H), 3.00(s, 3H), 3.77 (s, 3H), 4.04 (br, 1H), 6.48 (d, 1H), 6.84 (d, 1H), 6.88(dd, 1H), 6.96 (d, 1H), 7.16-7.22 (m, 1H), 7.32 (d, 1H), 7.36 (d, 1H),7.92 (d, 1H), 7.98 (br, 1H), 8.84 (br, 1H), and 10.74 (br, 1H).

Example 402 5-Bromo-6-chloro-pyridine-3-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide

5-Bromo-6-chloro-pyridine-3-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide(120 mg, 76%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 629 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 3.78 (s, 3H), 6.56(d, 1H), 6.88 (d, 1H), 6.78 (m, 1H), 6.88 (dd, 1H), 7.14 (d, 1H), 7.22(d, 1H), 7.36 (d, 1H), 8.02 (d, 1H), 8.12 (br, 1H), 8.33 (d, 1H), 8.73(d, 1H), 9.78 (br, 1H), and 10.74 (br, 1H).

Example 403 3,5-Dimethyl-isoxazole-4-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide

3,5-Dimethyl-isoxazole-4-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide(98 mg, 73%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 534 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 2.88 (s, 3H), 3.00(s, 3H), 3.75 (s, 3H), 5.21 (br, 1H), 6.54 (d, 1H), 6.80-6.88 (m, 1H),6.96 (m, 1H), 7.10-7.20 (m, 1H), 7.38 (d, 1H), 7.52 (d, 1H), 7.72 (br,1H), 8.01 (d, 1H), 8.22 (d, 1H), and 10.74 (br, 1H).

Example 404 5-Chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide

5-Chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide(111 mg, 79%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 568 (M+1)⁺; ¹H NMR (400 MHz, CDCl₃): δ 2.32 (s, 3H), 2.63(s, 3H), 3.74 (s, 3H), 6.48 (d, 1H), 6.76-6.84 (m, 1H), 6.94 (d, 1H),7.06-7.18 (m, 1H), 7.22 (d, 1H), 7.38 (d, 1H), 7.52 (d, 1H), 7.94 (d,1H), 8.08 (d, 1H), 8.20 (br, 1H), and 11.16 (br, 1H).

Example 405 6-Morpholin-4-yl-pyridine-3-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide

6-Morpholin-4-yl-pyridine-3-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide(115 mg, 76%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 601 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 2.15 (m, 4H), 3.60(t, 2H), 3.70 (t, 2H), 3.76 (s, 3H), 6.42 (d, 1H), 6.78 (d, 2H), 6.84(d, 1H), 6.96 (d, 1H), 7.04 (m, 2H), 7.20 (m, 1H), 7.34 (d, 1H), 7.79(d, 1H), 8.02 (d, 1H), 8.39 (d, 1H), 8.52 (br, 1H), and 11.28 (br, 1H).

Example 406 6-Oxazol-5-yl-pyridine-3-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide

6-Oxazol-5-yl-pyridine-3-sulfonic acid[4-(2-fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-amide(96 mg, 66%) was prepared from1-[5-amino-2-(2-fluoro-6-methoxy-phenoxy)-phenyl]-3-thiazol-2-yl-urea(94 mg, 0.25 mmol) following the general procedure L.

LC-MS (m/z): 583 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 3.77 (s, 3H), 6.46(d, 1H), 6.78-6.86 (m, 2H), 6.94 (d, 1H), 6.92-6.99 (m, 2H), 7.20 (q,1H), 7.33 (dd, 1H), 7.55 (d, 1H), 7.80 (d, 1H), 7.86-7.92 (m, 2H), 8.05(d, 1H), 8.18 (d, 1H), 9.88 (br, 1H), and 11.16 (br, 1H).

Example 4072-(2-{3-[2-(2-Fluoro-6-methoxy-phenoxy)-5-methanesulfonylamino-phenyl]-ureido}-thiazol-4-yl)-N-methyl-acetamide

(2-{3-[2-(2-Fluoro-6-methoxy-phenoxy)-5-methanesulfonylamino-phenyl]-ureido}-thiazol-4-yl)-N-methyl-acetamide(47 mg, 87.9%) was prepared from(2-{3-[2-(2-fluoro-6-methoxy-phenoxy)-5-methanesulfonylamino-phenyl]-ureido}-thiazol-4-yl)-aceticacid (51 mg, 0.10 mmol) following the general procedure K.

LC-MS (m/z): 524 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 2.93 (s, 3H), 3.48(d, 3H), 3.56 (s, 2H), 4.02 (s, 3H), 4.82 (br, 1H), 6.76 (d, 1H), 7.04(s, 1H), 7.09 (dd, 1H), 7.16 (t, 1H), 7.22 (d, 1H), 7.52 (q, 1H), 8.12(br, 1H), 8.44 (d, 1H), 9.88 (br, 1H) and 11.84 (br, 1H).

Example 408[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-carbamicacid tert-butyl ester

[4-(2-Fluoro-6-methoxy-phenoxy)-3-(3-thiazol-2-yl-ureido)-phenyl]-carbamicacid tert-butyl ester (4.56 g, 96.2%) was prepared from3-amino-4-(2-fluoro-6-methoxy-phenoxy)-phenyl)-carbamic acid tert-butylester (3.48 g, 10.0 mmol) following the general procedure D.

LC-MS (m/z): 475 (M+1)⁺; ¹H NMR (400 MHz, CD₃OD): δ 1.74 (s, 9H), 3.74(s, 3H), 6.64 (d, 1H), 6.92 (dd, 1H), 7.02 (d, 1H), 7.14 (m, 1H), 7.34(dd, 1H), 7.68 (dd, 1H), 7.88 (br, 1H), 8.32 (dd, 1H), 8.46 (d, 1H),9.26 (br, 1H), 11.62 (br, 1H).

Example 409 1-(4-Methyl-2-propoxy-phenyl)-3-thiazol-2-yl-urea

3-Propoxy-4-nitrotoluene (0.79 g, 80%) was prepared from 1-propanol and3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol) following the generalprocedure G. This was reduced to 4-methyl-2-propoxyaniline (0.54 g, 82%)following general procedure C.1-(4-Methyl-2-propoxy-phenyl)-3-thiazol-2-yl-urea (220 mg, 75%) wasprepared from 4-methyl-2-propoxyaniline (165 mg, 1.0 mmol) and2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

LC-MS (m/z): 292 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.03 (t, 3H), 1.80(m, 2H), 2.25 (s; 3H), 3.98 (t, 2H), 6.70 (dd, 1H), 6.83 (d, 1H), 7.10(d, 1H), 7.37 (d, 1H), 7.98 (d, 1H), 8.50 (br, 1H), 11.27 (br, 1H).

Example 410 1-(2-Butoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-(1-Butoxy)-4-nitrotoluene (0.78 g, 75%) was prepared from 1-butanoland 3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol) following the generalprocedure G. This was reduced to 4-methyl-2-(1-butoxy)aniline (0.47 g,70%) following general procedure C.1-(2-Butoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea (210 mg, 70%) wasprepared from 4-methyl-2-(1-butoxy)aniline (179 mg, 1.0 mmol) and2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

LC-MS (m/z): 306 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 0.95 (t, 3H), 1.52(m, 2H), 1.78 (m, 2H), 2.25 (s, 3H), 4.04 (t, 2H), 6.71 (dd, 1H), 6.86(d, 1H), 7.11 (d, 1H), 7.36 (d, 1H), 7.96 (d, 1H), 8.50 (br, 1H), 11.26(br, 1H).

Example 411 1-[4-Methyl-2-(3-methyl-butoxy)-phenyl]-3-thiazol-2-yl-urea

3-(3-Methyl-butoxy)-4-nitrotoluene (0.89 g, 80%) was prepared from3-methylbutanol and 3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol) followingthe general procedure G. This was reduced to4-methyl-2-(3-methylbutoxy)aniline (0.55 g, 72%) following generalprocedure C. 1-[4-Methyl-2-(3-methyl-butoxy)-phenyl]-3-thiazol-2-yl-urea(240 mg, 76%) was prepared from 4-methyl-2-(3-methyl-butoxy)aniline (193mg, 1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following thegeneral procedure D.

LC-MS (m/z): 320 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 0.94 (d, 6H), 1.71(m, 2H), 1.85 (m, 1H), 2.26 (s, 3H), 4.04 (t, 2H), 6.70 (d, 1H), 6.87(s, 1H), 7.11 (d, 1H), 7.36 (d, 1H), 7.96 (d, 1H), 8.50 (br, 1H), 11.26(br, 1H).

Example 412 1-(2-Allyloxy-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-Allyloxy-4-nitrotoluene (0.67 g, 70%) was prepared from allyl alcoholand 3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol) following the generalprocedure G. This was reduced to 4-methyl-2-(allyloxy)aniline (0.40 g,70%) following general procedure B.1-(2-Allyloxy-4-methyl-phenyl)-3-thiazol-2-yl-urea (196 mg, 68%) wasprepared from 4-methyl-2-(2-methylpropoxy)aniline (163 mg, 1.0 mmol) and2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

LC-MS (m/z): 290 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 2.25 (s, 3H), 4.64(d, 2H), 5.30 (m, 1H), 5.49 (m, 1H), 6.09 (m, 1H), 6.74 (dd, 1H), 6.87(s, 1H), 7.10 (d, 1H), 7.36 (dd, 1H), 7.97 (d, 1H), 8.60 (br, 1H), 11.15(br, 1H).

Example 4131-[4-Methyl-2-(2-methyl-allyloxy)-phenyl]-3-thiazol-2-yl-urea

3-(2-Methyl-allyloxy)-4-nitrotoluene (0.78 g, 75%) was prepared frommethallyl alcohol and 3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol)following the general procedure G. This was reduced to4-methyl-2-(2-methyl-allyloxy)aniline (0.47 g, 70%) following generalprocedure B.1-[4-Methyl-2-(2-methyl-allyloxy)-phenyl]-3-thiazol-2-yl-urea (210 mg,70%) was prepared from 4-methyl-2-(2-methyl-allyloxy)aniline (179 mg,1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following the generalprocedure D.

LC-MS (m/z): 304 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.83 (s, 3H), 2.25(s, 3H), 4.54 (s, 2H), 5.00 (s, 1H), 5.15 (s, 1H), 6.72 (d, 1H), 6.86(s, 1H), 7.10 (d, 1H), 7.36 (d, 1H), 7.97 (d, 1H), 8.60 (br, 1H), 11.21(br, 1H).

Example 4141-[4-Methyl-2-(3-methyl-but-2-enyloxy)-phenyl]-3-thiazol-2-yl-urea

3-(3-methyl-but-2-enyloxy)-4-nitrotoluene (0.8 g, 72%) was prepared from3-methylbut-2-en-1-ol and 3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol)following the general procedure G. This was reduced to4-methyl-2-(3-methyl-but-2-enyloxy)aniline (0.43 g, 62%) followinggeneral procedure B.1-[4-Methyl-2-(3-methyl-but-2-enyloxy)-phenyl]-3-thiazol-2-yl-urea (206mg, 65%) was prepared from 4-methyl-2-(3-methyl-but-2-enyloxy)aniline(191 mg, 1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following thegeneral procedure D.

LC-MS (m/z): 318 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.75 (d, 6H), 2.25(s, 3H), 4.60 (d, 2H), 5.26 (t, 1H), 6.71 (d, 1H), 6.89 (s, 1H), 7.09(d, 1H), 7.35 (d, 1H), 7.96 (dd, 1H), 8.56 (br, 1H), 11.17 (br, 1H).

Example 415 1-(2-Isopropoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-(2-Isopropoxy)-4-nitrotoluene (0.72 g, 74%) was prepared from2-propanol and 3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol) following thegeneral procedure G. This was reduced to 2-isopropoxy-4-methyl-aniline(0.42 g, 70%) following general procedure C.1-(2-Isopropoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea (180 mg, 62%) wasprepared from 2-isopropoxy-4-methyl-aniline (165 mg, 1.0 mmol) and2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

LC-MS (m/z): 292 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.32 (d, 6H), 2.24(s, 3H), 4.63 (m, 1H), 6.70 (dd, 1H), 6.88 (d, 1H), 7.10 (d, 1H), 7.37(d, 1H), 7.97 (d, 1H), 8.60 (br, 1H), 11.27 (br, 1H).

Example 416 1-(2-Cyclopentyloxy-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-Cyclopentyloxy-4-nitrotoluene (0.68 g, 62%) was prepared fromcyclopentanol and 3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol) followingthe general procedure G. This was reduced to2-cyclopentyloxy-4-methyl-aniline (0.43 g, 70%) following generalprocedure C. 1-(2-Cyclopentyloxy-4-methyl-phenyl)-3-thiazol-2-yl-urea(220 mg, 70%) was prepared from 2-cyclopentyloxy-4-methyl-aniline (191mg, 1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following thegeneral procedure D.

LC-MS (m/z): 318 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.60 (m, 2H), 1.80(m, 4H), 1.93 (m, 2H), 2.25 (s, 3H), 4.86 (m, 1H), 6.68 (dd, 1H), 6.81(d, 1H), 7.10 (d, 1H), 7.37 (d, 1H), 7.97 (d, 1H), 8.40 (br, 1H), 11.31(br, 1H).

Example 417 1-(2-Cyclopropylmethoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-Cyclopropylmethoxy-4-nitrotoluene (0.77 g, 75%) was prepared fromcyclopropylmethanol and 3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol)following the general procedure G. This was reduced to2-cyclopropylmethoxy-4-methyl-aniline (0.47 g, 71%) following generalprocedure C.1-(2-Cyclopropylmethoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea (218 mg,72%) was prepared from 2-cyclopropylmethoxy-4-methyl-aniline (177 mg,1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following the generalprocedure D.

LC-MS (m/z): 304 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 0.37 (m, 2H), 0.59(m, 2H), 1.29 (m, 1H), 2.24 (s, 3H), 3.88 (d, 2H), 6.71 (d, 1H), 6.84(d, 1H), 7.10 (d, 1H), 7.37 (d, 1H), 7.96 (d, 1H), 8.60 (br, 1H), 11.25(br, 1H).

Example 4181-[4-Methyl-2-(tetrahydro-pyran-2-ylmethoxy)-phenyl]-3-thiazol-2-yl-urea

4-Nitro-3-(tetrahydro-pyran-2-ylmethoxy)-toluene (0.80 g, 64%) wasprepared from tetrahydropyran-2-ylmethanol and 3-fluoro-4-nitrotoluene(0.77 g, 5.0 mmol) following the general procedure G. This was reducedto 4-methyl-2-(tetrahydro-pyran-2-ylmethoxy)-aniline (0.50 g, 71%)following general procedure C.1-[4-Methyl-2-(tetrahydro-pyran-2-ylmethoxy)-phenyl]-3-thiazol-2-yl-urea(246 mg, 71%) was prepared from4-methyl-2-(tetrahydro-pyran-2-ylmethoxy)-aniline (221 mg, 1.0 mmol) and2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

LC-MS (m/z): 348 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.34 (m, 1H), 1.50(m, 2H), 1.55 (m, 1H), 1.75 (d, 1H), 1.83 (m, 1H), 2.25 (s, 3H), 3.43(m, 1H), 3.90 (m, 2H), 4.01 (m, 1H), 6.72 (d, 1H), 6.86 (d, 1H), 7.10(d, 1H), 7.37 (d, 1H), 7.96 (d, 1H), 8.50 (br, 1H), 11.28 (br, 1H).

Example 4191-[4-Methyl-2-(tetrahydro-furan-2-ylmethoxy)-phenyl]-3-thiazol-2-yl-urea

4-Nitro-3-(tetrahydro-furan-2-ylmethoxy)-toluene (0.88 g, 75%) wasprepared from tetrahydro-furan-2-ylmethanol and 3-fluoro-4-nitrotoluene(0.77 g, 5.0 mmol) following the general procedure G. This was reducedto 4-methyl-2-(tetrahydro-furan-2-ylmethoxy)-aniline (0.50 g, 65%)following general procedure C.1-[4-Methyl-2-(tetrahydro-furan-2-ylmethoxy)-phenyl]-3-thiazol-2-yl-urea(236 mg, 71%) was prepared from4-methyl-2-(tetrahydro-furan-2-ylmethoxy)-aniline (207 mg, 1.0 mmol) and2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

LC-MS (m/z): 334 (M+1)⁺.

Example 420 1-(2-Cyclopentylmethoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-Cyclopentylmethoxy-4-nitrotoluene (0.82 g, 70%) was prepared fromcyclopentylmethanol and 3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol)following the general procedure G. This was reduced to2-cyclopentylmethoxy-4-methyl-aniline (0.58 g, 81%) following generalprocedure C.1-(2-Cyclopentylmethoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea (225 mg,68%) was prepared from 2-cyclopentylmethoxy-4-methyl-aniline (205 mg,1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following the generalprocedure D.

LC-MS (m/z): 332 (M+1)⁺;

Example 421{2-[3-(2-Cyclopropylmethoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

{2-[3-(2-Cyclopropylmethoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (253 mg, 65%) was prepared from2-cyclopropylmethoxy-4-methyl-aniline (177 mg, 1.0 mmol) and(2-amino-thiazol-4-yl)-acetic acid ethyl ester (186 mg, 1.0 mmol)following the general procedure D.

LC-MS (m/z): 390 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 0.36 (m, 2H), 0.59(m, 2H), 1.18 (t, 3H), 1.28 (m, 1H), 2.24 (s, 3H), 3.64 (s, 2H), 3.88(d, 2H), 4.08 (q, 2H), 6.71 (dd, 1H), 6.83 (d, 1H), 6.86 (d, 1H), 7.94(d, 1H), 8.40 (br, 1H), 11.36 (br, 1H).

{2-[3-(2-Cyclopropylmethoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid (165 mg, 92%) was prepared from{2-[3-(2-cyclopropylmethoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (195 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 362 (M+1)⁺.

Example 422{2-[3-(2-Cyclopentyloxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

{2-[3-(2-Cyclopentyloxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (250 mg, 62%) was prepared from2-cyclopentyloxy-4-methyl-aniline (191 mg, 1.0 mmol) and(2-amino-thiazol-4-yl)-acetic acid ethyl ester (186 mg, 1.0 mmol)following the general procedure D.{2-[3-(2-Cyclopentyloxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid (170 mg, 91%) was prepared from{2-[3-(2-cyclopropylmethoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (200 mg, 0.5 mmol) following the general procedure J.

LC-MS (m/z): 376 (M+1)⁺.

Example 4231-(2-Isobutoxy-4-methanesulfonylmethyl-phenyl)-3-thiazol-2-yl-urea

2-Isobutoxy-4-methanesulfonylmethyl-1-nitro-benzene (0.93 g, 65%) wasprepared from 2-methylpropanol and2-fluoro-4-methanesulfonylmethyl-1-nitro-benzene (1.16 g, 5.0 mmol)following the general procedure G. This was reduced to2-isobutoxy-4-methanesulfonylmethyl-aniline (0.46 g, 56%) followinggeneral procedure B.1-(2-Isobutoxy-4-methanesulfonylmethyl-phenyl)-3-thiazol-2-yl-urea (250mg, 65%) was prepared from 2-isobutoxy-4-methanesulfonylmethyl-aniline(257 mg, 1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following thegeneral procedure D.

LC-MS (m/z): 384 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.06 (d, 6H), 2.14(m, 1H), 2.88 (s, 3H), 3.11 (s, 2H), 4.39 (d, 2H), 6.19 (s, 1H), 6.89(d, 1H), 7.14 (s, 1H), 7.39 (d, 1H), 8.13 (d, 1H), 8.50 (br, 1H), 11.24(br, 1H).

Example 424(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetylamino)-aceticacid

(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetylamino)-aceticacid (90 mg, 86%) was prepared from(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetylamino)-aceticacid methyl ester (108 mg, 0.25 mmol) following the general procedure J.(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetylamino)-aceticacid methyl ester (150 mg, 70%) was in turn prepared from{2-[3-(2-isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetic acid(1.81 mg, 0.5 mmol) and glycine methyl ester hydrochloride following thegeneral procedure K.

LC-MS (m/z): 421 (M+1)⁺.

Example 425 1-(5-Formyl-2-isobutoxy-phenyl)-3-thiazol-2-yl-urea

4-(2-Methylpropoxy)-3-nitrobenzaldehyde (0.83 g, 75%) was prepared from2-methyl-propanol (0.46 ml, 5.0 mmol) and 4-fluoro-3-nitrobenzaldehyde(0.77 g, 5.0 mmol) following the general procedure G. This was reducedto 5-formyl-2-(2-methylpropoxy)-aniline (0.49 g, 68%) following generalprocedure B. 1-(5-Formyl-2-isobutoxy-phenyl)-3-thiazol-2-yl-urea (208mg, 65%) was prepared from 5-formyl-2-(2-methylpropoxy)aniline (193 mg,1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following the generalprocedure D.

LC-MS (m/z): 320 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.06 (d, 6H), 2.16(m, 1H), 3.96 (d, 2H), 7.16 (d, 1H), 7.25 (d, 1H), 7.40 (dd, 1H), 7.61(d, 1H), 8.69 (s, 1H), 9.86 (s, 1H), 10.75 (br, 1H), 11.51 (br, 1H).

Example 4262-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-N-(2-methoxy-ethyl)-acetamide

2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-N-(2-methoxy-ethyl)-acetamide(130 mg, 62%) was prepared from{2-[3-(2-isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetic acid(181 mg, 0.5 mmol) and 2-methoxyethylamine following the generalprocedure K.

LC-MS (m/z): 421 (M+1)⁺.

Example 427 1-(5-Fluoro-2-isobutoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea

2-Fluoro-5-(2-methylpropoxy)-4-nitrotoluene (0.73 g, 65%) was preparedfrom 2-methylpropanol (0.46 ml, 5.0 mmol) and2,5-difluoro-4-nitrotoluene (0.86 g, 5.0 mmol) following the generalprocedure G. This was reduced to5-fluoro-4-methyl-2-(2-methylpropoxy)-aniline (0.45 g, 70%) followinggeneral procedure C.1-(5-Fluoro-2-isobutoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea (205 mg,64%) was prepared from 5-fluoro-4-methyl-2-(2-methylpropoxy)-aniline(197 mg, 1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following thegeneral procedure D.

LC-MS (m/z): 324 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.03 (d, 6H), 2.16(m, 1H), 2.17 (s, 3H), 3.80 (d, 2H), 6.92 (d, 1H), 7.14 (d, 1H), 7.38(d, 1H), 7.93 (d, 1H), 8.50 (br, 1H), 11.44 (br, 1H).

Example 428 1-(5-Fluoro-2-isobutoxy-phenyl)-3-thiazol-2-yl-urea

5-Fluoro-2-(2-methylpropoxy)-4-nitrobenzene (0.83 g, 78%) was preparedfrom 2-methylpropanol (0.46 ml, 5.0 mmol) and2,5-difluoro-4-nitrobenzene (0.80 g, 5.0 mmol) following the generalprocedure G. This was reduced to 5-fluoro-2-(2-methylpropoxy)-aniline(0.58 g, 81%) following general procedure C.1-(5-Fluoro-2-isobutoxy-phenyl)-3-thiazol-2-yl-urea (220 mg, 72%) wasprepared from 5-fluoro-2-(2-methylpropoxy)-aniline (183 mg, 1.0 mmol)and 2-aminothiazole (100 mg, 1.0 mmol) following the general procedureD.

LC-MS (m/z): 310 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.03 (d, 6H), 2.11(m, 1H), 3.80 (d, 2H), 6.79 (m, 1H), 6.99 (m, 1H), 7.15 (d, 1H), 7.39(d, 1H), 8.01 (dd, 1H), 8.60 (br, 1H), 11.52 (br, 1H).

Example 429 1-(2-Isobutylsulfanyl-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-(Isobutylsulfanyl)-4-nitrotoluene (0.75 g, 67%) was prepared from2-methyl-propanethiol and 3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol)following the general procedure A. This was reduced to2-isobutylsulfanyl-4-methyl-aniline (0.46 g, 63%) following generalprocedure B. 1-(2-Isobutylsulfanyl-4-methyl-phenyl)-3-thiazol-2-yl-urea(218 mg, 68%) was prepared from 2-isobutylsulfanyl-4-methyl-aniline (195mg, 1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following thegeneral procedure D.

LC-MS (m/z): 318 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 0.85 (m, 6H), 1.40(m, 1H), 2.26 (s, 3H), 2.80 (m, 2H), 7.11 (s, 1H), 7.29 (s, 1H), 7.38(d, 1H), 7.89 (d, 1H), 8.65 (br, 1H), 11.28 (br, 1H).

Example 430{2-[3-(2-Isobutylsulfanyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

{2-[3-(2-Isobutylsulfanyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (276 mg, 68%) was prepared from2-isobutylsulfanyl-4-methyl-aniline (195 mg, 1.0 mmol) and ethyl2-amino-4-thiazolylacetate (186 mg, 1.0 mmol) following the generalprocedure D. Hydrolysis of this ester following general procedure J gave{2-[3-(2-isobutylsulfanyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid (230 mg, 90%).

LC-MS (m/z): 380 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 0.85 (m, 6H), 1.49(m, 1H), 2.26 (s, 3H), 2.83 (m, 2H), 3.56 (s, 2H), 6.85 (s, 1H), 7.09(d, 1H), 7.29 (d, 1H), 7.89 (d, 1H), 8.65 (br, 1H), 11.28 (br, 2H).

Example 4311-(2-Cyclopentanesulfinyl-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-Cyclopentanesulfanyl-4-nitrotoluene (0.47 g, 2.0 mmol) was oxidized to3-cyclopentanesulfinyl-4-nitrotoluene (0.46 g, 91%) following generalprocedure R (using one equivalent of m-CPBA).3-Cyclopentanesulfinyl-4-nitrotoluene was reduced to2-cyclopentanesulfinyl-4-methyl-aniline (0.33 g, 81%) following generalprocedure C.1-(2-Cyclopentanesulfinyl-4-methyl-phenyl)-3-thiazol-2-yl-urea (225 mg,65%) was prepared from 2-cyclopentanesulfinyl-4-methyl-aniline (223 mg,1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following the generalprocedure D.

LC-MS (m/z): 350 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.58 (m, 6H), 1.78(m, 1H), 1.94 (m, 1H), 2.34 (s, 3H), 3.43 (m, 1H), 7.11 (d, 1H), 7.33(dd, 1H), 7.36 (dd, 1H), 7.43 (s, 1H), 7.80 (d, 1H), 8.93 (br, 1H),11.25 (br, 1H).

Example 4321-(2-Cyclopentanesulfonyl-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-Cyclopentanesulfanyl-4-nitrotoluene (0.83 g, 70%) was prepared fromcyclopentyl mercaptan and 3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol)following the general procedure A. This was oxidized to3-cyclopentanesulfonyl-4-nitrotoluene (0.84 g, 90%) following generalprocedure R. 3-Cyclopentanesulfonyl-4-nitrotoluene was reduced to2-cyclopentanesulfonyl-4-methyl-aniline (0.53 g, 70%) following generalprocedure C.1-(2-Cyclopentanesulfonyl-4-methyl-phenyl)-3-thiazol-2-yl-urea (225 mg,62%) was prepared from 2-cyclopentanesulfonyl-4-methyl-aniline (239 mg,1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following the generalprocedure D.

LC-MS (m/z): 366 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.58 (m, 2H), 1.78(m, 2H), 1.86 (m, 2H), 2.04 (m, 2H), 2.38 (s, 3H), 3.54 (m, 1H), 6.94(d, 1H), 7.43 (dd, 1H), 7.61 (d, 1H), 7.67 (d, 1H), 8.18 (d, 1H), 9.20(br, 1H), 11.25 (br, 1H).

Example 433{2-[3-(2-Cyclopentanesulfonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

{2-[3-(2-Cyclopentanesulfonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (305 mg, 68%) was prepared from2-cyclopentanesulfonyl-4-methyl-aniline (239 mg, 1.0 mmol) and ethyl2-amino-4-thiazolylacetate (186 mg, 1.0 mmol) following the generalprocedure D.

LC-MS (m/z): 452 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 1.19 (t, 3H), 1.58(m, 4H), 1.84 (m, 4H), 2.35 (s, 3H), 3.65 (s, 2H), 3.77 (m, 1H), 4.08(q, 2H), 6.91 (s, 1H), 7.52 (d, 1H), 7.63 (s, 1H), 8.00 (d, 1H), 8.91(br, 1H), 11.89 (br, 1H).

Example 434{2-[3-(2-Cyclopentanesulfonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

Following the general procedure J,{2-[3-(2-cyclopentanesulfonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (225 mg, 0.5 mmol) was hydrolyzed to afford{2-[3-(4-methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-aceticacid (193 mg, 92%).

LC-MS (m/z): 424 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 1.60 (m, 4H), 1.84(m, 4H), 2.36 (s, 3H), 3.57 (s, 2H), 3.77 (m, 1H), 6.87 (s, 1H), 7.52(d, 1H), 7.63 (s, 1H), 8.01 (d, 1H), 8.95 (br, 1H), 12.32 (br, 2H).

Example 4352-{2-[3-(2-Cyclopentanesulfonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-N-methyl-acetamide

2-{2-[3-(2-Cyclopentanesulfonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-N-methyl-acetamide(30 mg, 68%) was prepared from{2-[3-(4-methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-aceticacid (42 mg, 0.1 mmol) and methylamine following the general procedureK.

LC-MS (m/z): 437 (M+1)⁺.

Example 4362-{2-[3-(2-Cyclopentanesulfonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-N-(2-methoxy-ethyl)-acetamide

2-{2-[3-(2-Cyclopentanesulfonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-N-methyl-acetamide(30 mg, 68%) was prepared from{2-[3-(4-methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-aceticacid (42 mg, 0.1 mmol) and 2-methoxyethylamine following the generalprocedure K.

LC-MS (m/z): 480 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 1.60 (m, 4H), 1.84(m, 4H), 2.36 (s, 3H), 3.21 (m, 4H), 3.24 (s, 3H), 3.43 (s, 2H), 3.76(m, 1H), 6.81 (s, 1H), 7.52 (d, 1H), 7.63 (s, 1H), 8.05 (br, 2H), 8.95(br, 1H), 11.85 (br, 1H).

Example 437 1-(2-Cyclopentylamino-4-methyl-phenyl)-3-thiazol-2-yl-urea

2-Cyclopentylamino-4-methyl-aniline (0.64 g, 68%) was prepared fromcyclopentylamine (1.0 ml, 10.0 mmol) and 3-fluoro-4-nitrotoluene (0.77g, 5.0 mmol) following the general procedure W.1-(2-Cyclopentylamino-4-methyl-phenyl)-3-thiazol-2-yl-urea (195 mg, 62%)was prepared from 2-cyclopentylamino-4-methyl-aniline (190 mg, 1.0 mmol)and 2-aminothiazole (100 mg, 1.0 mmol) following the general procedureD.

LC-MS (m/z): 317 (M+1)⁺, ¹H NMR (400 MHz, CDCl₃): δ 1.46 (m, 2H), 1.59(m, 2H), 1.68 (m, 2H), 2.01 (m, 2H), 2.32 (s, 3H), 3.78 (m, 1H), 6.51(d, 1H), 6.56 (s, 1H), 6.88 (d, 1H), 7.07 (br, 1H), 7.31 (d, 1H), 9.30(br, 1H), 10.72 (br, 1H).

Example 438 1-(2-Isobutylamino-4-methyl-phenyl)-3-thiazol-2-yl-urea

2-Isobutylamino-4-methyl-aniline (0.61 g, 69%) was prepared fromisobutylamine (0.73 g, 10.0 mmol) and 3-fluoro-4-nitrotoluene (0.77 g,5.0 mmol) following the general procedure W.1-(2-Isobutylamino-4-methyl-phenyl)-3-thiazol-2-yl-urea (196 mg, 65%)was prepared from 2-Isobutylamino-4-methyl-aniline (178 mg, 1.0 mmol)and 2-aminothiazole, (100 mg, 1.0 mmol) following the general procedureD.

LC-MS (m/z): 305 (M+1)⁺, ¹H NMR (400 MHz, CDCl₃): δ 0.95 (d, 6H), 1.88(m, 1H), 2.31 (s, 3H), 2.92 (d, 2H), 4.15 (br, 1H), 6.51 (m, 2H), 6.87(d, 1H), 7.08 (m, 1H), 7.31 (d, 1H), 9.30 (br, 1H), 10.72 (br, 1H).

Example 4391-[4-Methyl-2-(methyl-propyl-amino)-phenyl]-3-thiazol-2-yl-urea

4-Methyl-2-(methyl-propyl-amino)-aniline (0.56 g, 63%) was prepared fromN-methyl-propylamine (0.73 g, 10.0 mmol) and 3-fluoro-4-nitrotoluene(0.77 g, 5.0 mmol) following the general procedure W.1-[4-Methyl-2-(methyl-propyl-amino)-phenyl]-3-thiazol-2-yl-urea (215 mg,71%) was prepared from 4-methyl-2-(methyl-propyl-amino)-aniline (178 mg,1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following the generalprocedure D.

LC-MS (m/z): 305 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 0.85 (t, 3H), 1.40(m, 2H), 2.24 (s, 3H), 2.54 (s, 3H), 2.79 (t, 2H), 6.87 (dd, 1H), 7.02(d, 1H), 7.09 (d, 1H), 7.37 (d, 1H), 7.99 (d, 1H), 8.80 (br, 1H), 11.36(br, 1H).

Example 4401-[2-(Butyl-methyl-amino)-4-methyl-phenyl]-3-thiazol-2-yl-urea

4-Methyl-2-(butyl-methyl-amino)-aniline (0.62 g, 65%) was prepared fromN-methyl-butylamine (0.87 g, 10.0 mmol) and 3-fluoro-4-nitrotoluene(0.77 g, 5.0 mmol) following the general procedure W.1-[2-(Butyl-methyl-amino)-4-methyl-phenyl]-3-thiazol-2-yl-urea (220 mg,69%) was prepared from 4-methyl-2-(butyl-methyl-amino)-aniline (192 mg,1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following the generalprocedure D.

LC-MS (m/z): 319 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 0.82 (t, 3H), 1.27(m, 2H), 1.38 (m, 2H), 2.24 (s, 3H), 2.54 (s, 3H), 2.82 (t, 2H), 6.87(d, 1H), 7.02 (s, 1H), 7.09 (d, 1H), 7.37 (d, 1H), 7.97 (d, 1H), 8.80(br, 1H), 11.37 (br, 1H).

Example 441 1-(2-Diethylamino-4-methyl-phenyl)-3-thiazol-2-yl-urea

2-(Diethyl-amino)-4-methyl-aniline (0.63 g, 71%) was prepared fromdiethylamine (0.73 g, 10.0 mmol) and 3-fluoro-4-nitrotoluene (0.77 g,5.0 mmol) following the general procedure W.1-(2-Diethylamino-4-methyl-phenyl)-3-thiazol-2-yl-urea (188 mg, 62%) wasprepared from 2-(diethyl-amino)-4-methyl-aniline (178 mg, 1.0 mmol) and2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

LC-MS (m/z): 305 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 0.89 (t, 6H), 2.24(s, 3H), 2.90 (q, 4H), 6.92 (dd, 1H), 7.04 (d, 1H), 7.09 (d, 1H), 7.37(d, 1H), 8.04 (d, 1H), 9.00 (br, 1H), 11.44 (br, 1H).

Example 4421-[2-(Cyclopropylmethyl-propyl-amino)-4-methyl-phenyl]-3-thiazol-2-yl-urea

2-(Cyclopropylmethyl-propyl-amino)-4-methyl-aniline (0.68 g, 63%) wasprepared from N-propyl-cyclopropanemethylamine (1.13 g, 10.0 mmol) and3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol) following the generalprocedure W.1-[4-Methyl-2-(methyl-propyl-amino)-phenyl]-3-thiazol-2-yl-urea (210 mg,61%) was prepared from 4-methyl-2-(methyl-propyl-amino)-aniline (218 mg,1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following the generalprocedure D.

LC-MS (m/z): 345 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ −0.24 (m, 2H),0.30 (m, 2H), 0.80 (m, 4H), 1.32 (m, 2H), 2.24 (s, 3H), 2.69 (d, 2H),2.91 (t, 2H), 6.90 (dd, 1H), 7.07 (m, 2H), 7.37 (d, 1H), 8.01 (m, 1H),9.00 (br, 1H), 11.51 (br, 1H).

Example 4431-[2-(Isobutyl-methyl-amino)-4-methyl-phenyl]-3-thiazol-2-yl-urea

2-(Isobutyl-methyl-amino)-4-methyl-aniline (0.62 g, 65%) was preparedfrom N-isobutyl-methylamine (0.87 g, 10.0 mmol) and3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol) following the generalprocedure W.1-[2-(Isobutyl-methyl-amino)-4-methyl-phenyl]-3-thiazol-2-yl-urea (216mg, 68%) was prepared from 2-(isobutyl-methyl-amino)-4-methyl-aniline(192 mg, 1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following thegeneral procedure D.

LC-MS (m/z): 319 (M+1)⁺, ¹H NMR (400 MHz, CDCl₃): δ 0.86 (d, 6H), 1.68(m, 1H), 2.31 (s, 3H), 2.58 (s, 3H), 2.66 (d, 2H), 6.88 (d, 1H), 6.96(m, 2H), 7.44 (d, 1H), 8.12 (d, 1H), 9.20 (br, 1H), 11.36 (br, 1H).

Example 444(2-{3-[2-(Isobutyl-methyl-amino)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid ethyl ester

(2-{3-[2-(Isobutyl-methyl-amino)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid ethyl ester (290 mg, 72%) was prepared from2-(isobutyl-methyl-amino)-4-methyl-aniline (192 mg, 1.0 mmol) and ethyl2-amino-4-thiazolylacetate (186 mg, 1.0 mmol) following the generalprocedure D. Hydrolysis of this ester following the general procedure Jgave(2-{3-[2-(isobutyl-methyl-amino)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid (250 mg, 92%).

LC-MS (m/z): 377 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 0.85 (d, 6H), 1.60(m, 1H), 2.21 (s, 3H), 2.66 (m, 5H), 3.53 (s, 2H), 6.81 (s, 1H), 6.85(d, 1H), 6.99 (s, 1H), 7.95 (d, 1H), 8.60 (br, 1H), 11.55 (br, 1H),12.35 (br, 1H).

Example 4452-(2-{3-[2-(Isobutyl-methyl-amino)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-N-methyl-acetamide

2-(2-{3-[2-(Isobutyl-methyl-amino)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-N-methyl-acetamide(63 mg, 65%) was prepared from(2-{3-[2-(isobutyl-methyl-amino)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid (95 mg, 0.25 mmol) and methylamine following the general procedureK.

LC-MS (m/z): 390 (M+1)⁺, ¹H NMR (400 MHz, CDCl₃): δ 0.85 (d, 6H), 1.67(m, 1H), 2.29 (s, 3H), 2.63 (s, 3H), 2.75 (s, 2H), 2.80 (s, 3H), 3.62(s, 2H), 6.50 (br, 1H), 6.62 (s, 1H), 6.93 (m, 2H), 8.04 (d, 1H), 8.68(br, 1H), 10.00 (br, 1H).

Example 4462-(2-{3-[2-(Isobutyl-methyl-amino)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-N-(2-methoxy-ethyl)-acetamide

2-(2-{3-[2-(Isobutyl-methyl-amino)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-N-(2-methoxy-ethyl)-acetamide(78 mg, 72%) was prepared from(2-{3-[2-(isobutyl-methyl-amino)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid (95 mg, 0.25 mmol) and 2-methoxymethylamine following the generalprocedure K.

LC-MS (m/z): 434 (M+1)⁺.

Example 447 1-(4-Methyl-2-pyrrolidin-1-yl-phenyl)-3-thiazol-2-yl-urea

4-Methyl-2-(pyrrolidin-1-yl)aniline (0.57 g, 65%) was prepared frompyrrolidine (0.71 g, 10.0 mmol) and 3-fluoro-4-nitrotoluene (0.77 g, 5.0mmol) following the general procedure W.1-(4-Methyl-2-pyrrolidin-1-yl-phenyl)-3-thiazol-2-yl-urea (217 mg, 72%)was prepared from 4-methyl-2-(pyrrolidin-1-yl)aniline (176 mg, 1.0 mmol)and 2-aminothiazole (100 mg, 1.0 mmol) following the general procedureD.

LC-MS (m/z): 303 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 1.89 (m, 4H), 2.23(s, 3H), 3.02 (m, 4H), 6.75 (dd, 1H), 6.88 (d, 1H), 7.09 (d, 1H), 7.36(dd, 1H), 7.70 (d, 1H), 8.40 (br, 1H), 11.07 (br, 1H).

Example 4481-[2-(2,3-Dihydro-indol-1-yl)-5-fluoro-phenyl]-3-thiazol-2-yl-urea

2-(2,3-Dihydro-indol-1-yl)-5-fluoro-aniline (0.59 g, 52%) was preparedfrom indoline (0.6 g, 5.0 mmol) and 2,5-difluoro-nitrobenzene (0.80 g,5.0 mmol) following the general procedure W.1-[2-(2,3-Dihydro-indol-1-yl)-5-fluoro-phenyl]-3-thiazol-2-yl-urea (198mg, 56%) was prepared from 2-(2,3-dihydro-indol-1-yl)-5-fluoro-aniline(228 mg, 1.0 mmol) and 2-aminothiazole (100 mg, 1.0 mmol) following thegeneral procedure D.

LC-MS (m/z): 355 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 3.16 (t, 2H), 3.70(br, 2H), 6.10 (d, 1H), 6.73 (m, 1H), 6.94 (m, 2H), 7.14 (d, 1H), 7.22(d, 1H), 7.34 (m, 2H), 8.13 (dd, 1H), 9.01 (br, 1H), 11.32 (br, 1H).

Example 449 1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-thiazol-2-yl-urea

4-Methyl-2-(piperidin-1-yl)-aniline (0.63 g, 67%) was prepared frompiperidine (0.85 g, 10.0 mmol) and 3-fluoro-4-nitrotoluene (0.77 g, 5.0mmol) following the general procedure W.1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-thiazol-2-yl-urea (214 mg, 68%)was prepared from 4-methyl-2-(piperidin-1-yl)-aniline (190 mg, 1.0 mmol)and 2-aminothiazole (100 mg, 1.0 mmol) following the general procedureD.

LC-MS (m/z): 317 (M+1)⁺, ¹H NMR (400 MHz, CDCl₃): δ 1.49 (m, 2H), 1.69(m, 4H), 2.30 (s, 3H), 2.82 (t, 4H), 6.92 (m, 3H), 7.47 (d, 1H), 7.96(d, 1H), 8.90 (br, 1H), 11.36 (br, 1H).

Example 450{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (285 mg, 71%) was prepared from4-methyl-2-(piperidin-1-yl)-aniline (190 mg, 1.0 mmol) and ethyl2-amino-4-thiazolylacetate (186 mg, 1.0 mmol) following the generalprocedure D. Hydrolysis of this ester following general procedure J gave{2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-4-yl}-aceticacid (238 mg, 90%).

LC-MS (m/z): 375 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 1.53 (br, 2H),1.75 (m, 4H), 2.23 (s, 3H), 2.70 (m, 4H), 3.55 (s, 2H), 6.83 (s, 1H),6.87 (d, 1H), 6.99 (s, 1H), 7.92 (d, 1H), 8.40 (br, 1H), 11.28 (br, 1H),12.42 (br, 1H).

Example 4511-[2-(2-Fluoro-6-methoxy-phenoxy)-4-methyl-phenyl]-3-thiazol-2-yl-urea

3-(2-fluoro-6-methoxyphenoxy)-nitrotoluene (0.9 g, 65%) was preparedfrom 2-fluoro-6-methoxyphenol (0.78 g, 5.5 mmol) and3-fluoro-4-nitrotoluene (0.77 g, 5.0 mmol) following the generalprocedure A. This compound was reduced to4-fluoro-2-(2-fluoro-6-methoxyphenoxy)aniline (0.58 g, 72%) followingthe general procedure C.1-[2-(2-Fluoro-6-methoxy-phenoxy)-4-methyl-phenyl]-3-thiazol-2-yl-urea(122 mg, 65%) was prepared from2-(2-fluoro-6-methoxy-phenoxy)-4-methyl-aniline (124 mg, 0.5 mmol) and2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

LCMS (m/z): 374 (M+2)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 2.13 (s, 3H), 3.79(s, 3H), 6.30 (s, 1H), 6.83 (d, 1H), 7.07 (m, 3H), 7.34 (m, 2H), 8.06(d, 1H), 8.97 (br, 1H), 10.93 (s, 1H).

Example 4521-[2-(2-Fluoro-6-methoxy-phenoxy)-4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-thiazol-2-yl-urea

3-(2-fluoro-6-methoxyphenoxy)-nitrotoluene (0.28 g, 1.0 mmol) was heatedwith N-bromosuccinimide (200 mg, 1.1 mmol) and dibenzoyl peroxide (10mg) in CCl₄ (10 mL) at 90° C. for 3 hr. The reaction mixture was cooled,filtered and the filtrate was concentrated. To the residue was addedN-methylpiperizine (110 mg, 1.1 mmol) in THF (5 mL) and the mixture washeated at 60° C. for 4 hr. The volatiles were removed under reducedpressure. The residue was dissolved in ethyl acetate and washed (brine),dried (Na₂SO₄) and concentrated. The resulting nitrobenzene was reducedto2-(2-fluoro-6-methoxy-phenoxy)-4-(4-methyl-piperazin-1-ylmethyl)-aniline(224 mg, 65%) following the general procedure C.1-[2-(2-Fluoro-6-methoxy-phenoxy)-4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-thiazol-2-yl-urea(130 mg, 55%) was prepared from2-(2-fluoro-6-methoxy-phenoxy)-4-(4-methyl-piperazin-1-ylmethyl)-aniline(172 mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following thegeneral procedure D.

LCMS (m/z): 472 (M+2)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 2.12 (s, 3H), 2.24(br, 8H), 3.28 (s, 2H), 3.77 (s, 3H), 6.46 (s, 1H), 6.89 (d, 1H), 7.07(m, 3H), 7.34 (m, 2H), 8.11 (d, 1H), 9.02 (br, 1H), 10.96 (s, 1H).

Example 453(2-{3-[2-(2-Fluoro-6-methoxy-phenoxy)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid

(2-{3-[2-(2-Fluoro-6-methoxy-phenoxy)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid ethyl ester (330 mg, 72%) was prepared from2-(2-fluoro-6-methoxyphenoxy)-aniline (247 mg, 1.0 mmol) and ethyl2-amino-4-thiazolylacetate (186 mg, 1.0 mmol) following the generalprocedure D. Hydrolysis of this ester following general procedure J gave(2-{3-[2-(2-fluoro-6-methoxy-phenoxy)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-aceticacid (283 mg, 91%).

LCMS (m/z): 432 (M+2)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 2.13 (s, 3H), 3.55(s, 2H), 3.79 (s, 3H), 6.30 (s, 1H), 6.83 (d, 1H), 6.88 (s, 1H), 7.03(m, 2H), 7.34 (m, 1H), 8.04 (d, 1H), 9.05 (br, 1H), 11.02 (br, 2H).

Example 4541-[2-(2-Fluoro-6-methoxy-phenoxy)-5-formyl-phenyl]-3-thiazol-2-yl-urea

4-(2-Fluoro-6-methoxy-phenoxy)-3-nitrobenzaldehyde (1.0 g, 70%) wasprepared from 2-fluoro-6-methoxyphenol (0.78 g, 5.5 mmol) and4-fluoro-3-nitrobenzaldehyde (0.84 g, 5.0 mmol) following the generalprocedure A. This was reduced to5-formyl-2-(2-fluoro-6-methoxy-phenoxy)-aniline (0.57 g, 62%) followinggeneral procedure B.1-[2-(2-Fluoro-6-methoxy-phenoxy)-5-formyl-phenyl]-3-thiazol-2-yl-urea(265 mg, 69%) was prepared from5-formyl-2-(2-fluoro-6-methoxy-phenoxy)-aniline (261 mg, 1.0 mmol) and2-aminothiazole (100 mg, 1.0 mmol) following the general procedure D.

LC-MS (m/z): 388 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 3.80 (s, 3H), 6.71(d, 1H), 7.14 (m, 3H), 7.39 (m, 2H), 7.52 (dd, 1H), 8.78 (d, 1H), 9.31(br, 1H), 9.90 (s, 1H), 11.04 (s, 1H).

Example 4551-[2-(2-Fluoro-6-methoxy-phenoxy)-5-morpholin-4-ylmethyl-phenyl]-3-thiazol-2-yl-urea

1-[2-(2-Fluoro-6-methoxy-phenoxy)-5-morpholin-4-ylmethyl-phenyl]-3-thiazol-2-yl-urea(35 mg, 78%) was prepared from1-[2-(2-fluoro-6-methoxy-phenoxy)-5-formyl-phenyl]-3-thiazol-2-yl-urea(39 mg, 0.1 mmol) and morpholine following the general procedure O.

LC-MS (m/z): 459 (M+1)⁺, ¹H NMR (400 MHz, DMSO-d₆): δ 2.24 (s, 4H), 3.30(s, 2H), 3.48 (s, 4H), 3.77 (s, 3H), 6.48 (s, 1H), 6.93 (d, 1H), 7.10(m, 3H), 7.37 (m, 2H), 8.12 (d, 1H), 9.04 (br, 1H), 10.96 (br, 1H).

Example 4561-[2-(2-Fluoro-6-methoxy-phenoxy)-5-methanesulfonylmethyl-phenyl]-3-thiazol-2-yl-urea

4-(2-Fluoro-6-methoxyphenoxy)-3-nitrotoluene (0.28 g, 1.0 mmol) washeated with N-bromosuccinimide (200 mg, 1.1 mmol) and dibenzoyl peroxide(10 mg) in CCl₄ (10 mL) at 90° C. for 3 hr. The reaction mixture wascooled, filtered and the filtrate was concentrated. To this residue wasadded sodium methanesulfinate (110 mg, 1.1 mmol) in THF (5 mL) and themixture was heated at 60° C. for 4 hr. The volatiles were removed underreduced pressure. The residue was dissolved in ethyl acetate and waswashed (brine), dried (Na₂SO₄) and concentrated. The resultingnitrobenzene was reduced to2-(2-fluoro-6-methoxy-phenoxy)-5-methanesulfonylmethyl-aniline (210 mg,65%) following the general procedure B.1-[2-(2-Fluoro-6-methoxy-phenoxy)-5-methanesulfonylmethyl-phenyl]-3-thiazol-2-yl-urea(138 mg, 61%) was prepared from2-(2-fluoro-6-methoxy-phenoxy)-5-methanesulfonylmethyl-aniline (162 mg,0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the generalprocedure D.

LCMS (m/z): 452 (M+1)⁺; ¹H NMR (400 MHz, DMSO-d₆): δ 2.93 (s, 3H), 3.35(s, 2H), 3.80 (s, 3H), 6.52 (d, 1H), 6.93 (d, 1H), 7.07 (m, 3H), 7.35(m, 2H), 8.31 (s, 1H), 9.22 (br, 1H), 11.02 (s, 1H).

Example 457{5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

To a solution of{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (0.05 g, 0.12 mmol) in 2 ml of acetonitrile was addedN-chlorosuccinimide (0.018 g, 0.13 mmol). The reaction mixture wasstirred under nitrogen in a pressure bottle excluded from light for 1.5hour at 80° C. The mixture was diluted with 15 ml of DCM, washed (1NHCl, saturated NaHCO₃, water), dried (MgSO₄) and concentrated underreduced pressure. The crude product was purified by preparative HPLC toafford the title compound (0.08 g, 15%).

HPLC-MS (Method A): m/z=450, 452 (M+1)⁺; R_(t)=5.55 min.

¹H NMR (300 MHz, CDCl₃): δ 1.29 (t, J=7.2 Hz, 3H), 1.71 (m, 4H), 1.90(m, 4H), 2.37 (s, 3H), 3.70 (s, 2H), 3.75 (m, 1H), 4.24 (q, J=7.2 Hz,2H), 7.35 (d, J=7.9 Hz, 1H), 7.70 (s, 1H), 8.42 (d, J=8.3 Hz, 1H) and11.59 (s, 1H)

Example 458{5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

To a solution of{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (0.05 g, 0.12 mmol) in 2 ml of acetonitrile was addedN-bromosuccinimide (0.024 g, 0.13 mmol). The reaction mixture wasstirred under nitrogen in a pressure bottle excluded from lightovernight at 25° C. The mixture was diluted with 15 ml of DCM, washed(1N HCl, saturated NaHCO₃, water), dried (MgSO₄) and concentrated underreduced pressure. The crude product was purified by preparative HPLC toafford the title compound (0.013 g, 21%).

HPLC-MS (Method A): m/z=494, 496 (M+1)⁺; R_(t)=5.45 min.

¹H NMR (300 MHz, CDCl₃): δ 1.29 (t, J=7.2 Hz, 3H), 1.71 (m, 4H), 1.92(m, 4H), 2.38 (s, 3H), 3.73 (s, 2H), 3.77 (m, 1H), 4.23 (q, J=7.2 Hz,2H), 7.36 (dd, J=1.3, 8.5 Hz, 1H), 7.73 (s, 1H), 8.37 (d, J=8.3 Hz, 1H)and 11.81 (s, 1H).

Example 459{5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

To a suspension of{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid (0.50 g, 1.29 mmol) in 20 ml of acetonitrile was addedN-chlorosuccinimide (0.19 g, 1.42 mmol). The reaction mixture wasstirred under nitrogen, in a pressure bottle excluded from light, for 2h at 80° C. The mixture was concentrated under reduced pressure,dissolved in DMSO and purified by preparative HPLC to afford the titlecompound (0.128 g, 24%).

HPLC-MS (Method A): m/z=422, 424 (M+1)⁺; R_(t)=5.84 min.

¹H NMR (300 MHz, DMSO-d₆): δ 1.64 (m, 4H), 1.77 (m, 2H), 1.90 (m, 2H),1.90 (m, 2H), 2.34 (s, 3H), 3.56 (s, 2H), 3.88 (m, 1H), 7.40 (dd, J=1.5,8.7 Hz, 1H), 7.86 (d, J=1.1 Hz, 1H), 8.15 (d, J=8.3 Hz, 1H) and 10.69(s, 1H)

Example 460{5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

To a suspension of{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (0.20 g, 0.52 mmol) in 10 ml of acetic acid was addedN-bromosuccinimide (0.10 g, 0.57 mmol). The reaction mixture was stirredunder nitrogen in a pressure bottle excluded from light overnight at 25°C. The mixture was concentrated under reduced pressure, dissolved inDMSO and purified by preparative HPLC to afford the title compound(0.137 g, 57%).

HPLC-MS (Method A): m/z=466, 468 (M+1)⁺; R_(t)=4.59 min.

¹H NMR (300 MHz, DMSO-d₆): δ 1.64 (M, 4H), 1.76 (m, 2H), 1.89 (m, 2H),2.34 (s, 3H), 3.55 (s, 2H), 3.88 (m, 1H), 7.40 (d, J=8.3 Hz, 1H), 7.87(s, 1H), 8.15 (d, J=8.7 Hz, 1H), 10.71 (s, 1H) and 12.15 (s, 1H)

Example 461Bromo-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

To a solution of{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (0.05 g, 0.12 mmol) in 2 ml of acetonitrile was addedN-bromosuccinimide (0.024 g, 0.13 mmol). The reaction mixture wasstirred under nitrogen in a pressure bottle excluded from lightovernight at 25° C. The mixture was diluted with 15 ml of DCM, washed(1N HCl, saturated NaHCO₃, water), dried (MgSO₄) and concentrated underreduced pressure. The crude product was purified by preparative HPLC toafford the title compound (0.010 g, 17%).

HPLC-MS (Method A): m/z=494, 496 (M+1)⁺; R_(t)=5.19 min.

¹H NMR (300 MHz, CDCl₃): δ 1.33 (t, J=7.2 Hz, 3H), 1.71 (m, 4H), 1.92(m, 4H), 2.37 (s, 3H), 3.76 (m, 1H), 4.30 (dq, J=2.3, 7.2 Hz, 2H), 5.45(s, 1H), 7.17 (s, 1H), 7.36 (d, J=8.7 Hz, 1H), 7.73 (s, 1H), 8.40 (d,J=8.7 Hz, 1H) and 11.83 (s, 1H)

Example 462 General Procedure D{2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-acetic acidethyl ester

To a stirred solution of phenyl-carbamic acid tert-butyl ester (1.2 g,6.2 mmol) in Et₂O (12 mL) under a nitrogen atmosphere was added dropwisea 1.7 M solution of t-BuLi in pentan (8.4 mL, 14.3 mmol) over a 10-minperiod at −20° C. The mixture was stirred at −10° C. for 2.5 h and thencyclopentanecarboxylic acid methoxy-methyl-amide (1.07 g, 6.8 mmol) wasadded over 5 min. The mixture was allowed to warm to room temperatureand stirred for further 1 h before it was quenched with aqueous NH₄Cl.The organic phase was isolated and the aqueous phase was extracted withCH₂Cl₂, and the combined organic phases were dried and concentrated invacuo. The crude material was dissolved CH₂Cl₂ (18 mL) and TFA (6 mL)and stirred at room temperature for 2 h. The reaction mixture wasevaporated in vacuo, and added aqueous NaHCO₃ to pH 7 and extracted withCH₂Cl₂. The combined organic phases were dried and concentrated in vacuoto give 1.03 g (68%) of (2-amino-phenyl)-cyclopentyl-methanone as anoil.

The title compound (41 mg, 16%) was prepared from2-amino-phenyl-cyclopentyl-methanone (120 mg, 0.63 mmol) andethyl-2-amino-4-thiazolyl acetate (118 mg, 0.63 mmol) following thegeneral procedure D.

¹H NMR (400 MHz; CDCl₃): -1.28 (t, 3H), 1.66-1.77 (m, 4H), 1.84-1.96 (m,4H), 3.70 (s, 2H), 3.74 (brt, 1H), 4.20 (q, 2H), 6.72 (s, 1H), 7.10 (t,1H), 7.53 (t, 1H), 7.92 (d, 1H), 8.57 (br s, 1H), 11.78 (s, 1H);HPLC-MS: m/z=424.0 (M+23); R_(t)=4.45 min.

Example 463 General Procedure J{2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-acetic acid

The title compound (9 mg, 27%) was prepared from{2-[3-(2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-acetic acidethyl ester (208 mg, 0.5 mmol) following the general procedure J.

¹H NMR (400 MHz; Acetone d₆): δ 1.85-2.11 (m, 8H), 3.71 (s, 2H), 3.94(br t, 1H), 6.86 (s, 1H), 7.18 (t, 1H), 7.79 (t, 1H), 8.09 (d, 1H), 8.56(d, 1H), 11.36 (s, 1H); HPLC-MS m/z=396.1 (M+23); R_(t)=3.87 min.

Example 464 General Procedure AA{2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

To a stirred solution of (4-methoxy-phenyl)-carbamic acid tert-butylester (2.0 g, 9.0 mmol) in Et₂O (20 mL) under a nitrogen atmosphere wasadded dropwise a 1.7 M solution of t-BuLi in pentan (12.1 mL, 20.6 mmol)over a 10-min period at −20° C. The mixture was stirred at −15° C. for1.5 h and then cyclopentanecarboxylic acid methoxy-methyl-amide (1.55 g,9.9 mmol) was added over 5 min. The mixture was allowed to warm to roomtemperature and stirred for further 1 h before it was quenched withaqueous NH₄Cl. The organic phase was isolated and the aqueous phase wasextracted with CH₂Cl₂, and the combined organic phases were dried andconcentrated in vacuo. The crude material was dissolved CH₂Cl₂ (18 mL)and TFA (6 mL) and stirred at room temperature for 2 h. The reactionmixture was evaporated in vacuo, and added aqueous NaHCO3 to pH 7 andextracted with CH₂Cl₂, dried and concentrated to give a crude productwhich was purified by flash chromatography (Quad flash 25, EtOAc-heptane1:20->1:4). This gave 0.65 g (31%) of(2-amino-5-methoxy-phenyl)-cyclopentyl-methanone as an oil.

The title compound (158 mg, 80%) was prepared from(2-amino-5-methoxy-phenyl)-cyclopentyl-methanone (100 mg, 0.46 mmol) andethyl-2-amino-4-thiazolyl acetate (85 mg, 0.46 mmol) following thegeneral procedure AA.

¹H NMR (400 MHz; CDCl₃): δ 1.28 (t, 3H), 1.66-1.74 (m, 4H), 1.86-1.96(m, 4H), 3.68 (br t, 1H), 3.70 (s, 2H), 3.84 (s, 3H), 4.20 (q, 2H), 6.71(s, 1H), 7.10 (dd, 1H), 7.42 (d, 1H), 8.45 (br s, 1H), 9.13 (br s, 1H),11.31 (br s, 1H); HPLC-MS: m/z=454.1 (M+23); R_(t)=5.48 min.

Example 465 General Procedure J{2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-thiazol-4-yl}-aceticacid

The title compound (92 mg, 86%) was prepared from{2-[3-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (112 mg, 0.26 mmol) following the general procedure J.

¹H NMR (400 MHz; DMSO d₆): δ 1.58-1.65 (m, 4H), 1.70-1.92 (m, 4H), 3.57(s, 2H), 3.82 (s, 3H), 3.88 (br p, 1H), 6.84 (s, 1H), 7.19 (dd, 1H),7.44 (s, 1H), 8.08 (d, 1H), 10.22 (s, 1H), 12.05 (br s, 2H); HPLC-MS:m/z=426.1 (M+23); R_(t)=4.49 min.

Example 466 General Procedure AA{2-[3-(2-Cyclopropanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

To a stirred solution of p-tolyl-carbamic acid tert-butyl ester (1.0 g,4.8 mmol) in Et₂O (10 mL) under a nitrogen atmosphere was added dropwisea 1.7 M solution of t-BuLi in pentan (6.5 mL, 11.1 mmol) over a 10-minperiod at −20° C. The mixture was stirred at −10° C. for 2.5 h and thencyclopropanecarboxylic acid methoxy-methyl-amide (0.92 g, 6.3 mmol) wasadded over 5 min. The mixture was allowed to warm to room temperatureand stirred for further 1 h before it was quenched with aqueous NH₄Cl.The organic phase was isolated and the aqueous phase was extracted withCH₂Cl₂, and the combined organic phases were dried and concentrated invacuo. The crude material was dissolved CH₂Cl₂ (15 mL) and TFA (15 mL)and stirred at room temperature for 3 h. The reaction mixture wasevaporated in vacuo, and added aqueous NaHCO3 to pH 7 and extracted withCH₂Cl₂. The combined organic phases were dried and concentrated in vacuoto give 0.80 g crude (2-amino-5-methyl-phenyl)-cyclopropyl-methanone asa yellow oil.

The title compound (190 mg, 43%) was prepared from crude(2-amino-5-methyl-phenyl)-cyclopropyl-methanone (200 mg, 1.14 mmol) andethyl-2-amino-4-thiazolyl acetate (212 mg, 1.14 mmol) following thegeneral procedure AA.

¹H NMR (400 MHz; CDCl₃): δ 1.04-1.10 (m, 2H), 1.24-1.30 (m, 5H), 2.39(s, 3H), 2.62-2.72 (m, 1H), 3.73 (s, 2H), 4.20 (q, 2H), 6.78 (s, 1H),7.37 (dd, 1H), 7.89 (d, 1H), 8.37 (d, 1H), 9.42 (br s, 2H), 11.50 (s,1H); HPLC-MS: m/z=410.0 (M+23); R_(t)=4.11 min.

Example 467 General Procedure J{2-[3-(2-Cyclopropanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

The title compound (111 mg, 99%) was prepared from{2-[3-(2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-acetic acidethyl ester (120 mg, 0.31 mmol) following the general procedure J.

¹H NMR (400 MHz; DMSO d₆): δ 1.04 (br s, 4H), 2.38 (s, 3H), 2.76 (br s,1H), 3.58 (s, 2H), 6.86 (s, 1H), 6.92 (d, 1H), 8.02 (s, 1H), 8.14 (d,1H), 10.46 (s, 1H), 12.05 (br s, 2H); HPLC-MS: m/z=382.0 (M+23);R_(t)=3.38 min.

Example 468 General Procedure AA{2-[3-(2-Cyclobutanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

Crude (2-amino-5-methyl-phenyl)-cyclobutyl-methanone (80%, oil) wasprepared in a similar fashion as described for(2-amino-5-methyl-phenyl)-cyclopropyl-methanone usingcyclobutanecarboxylic acid methoxy-methyl-amide instead ofcyclopropanecarboxylic acid methoxy-methyl-amide.

The title compound (210 mg, 49%) was prepared from crude(2-amino-5-methyl-phenyl)-cyclobutyl-methanone (200 mg, 1.06 mmol) andethyl-2-amino-4-thiazolyl acetate (197 mg, 1.06 mmol) following thegeneral procedure AA.

¹H NMR (400 MHz; CDCl₃): δ 1.30 (t, 3H), 1.83-2.50 (m, 6H), 2.36 (s,3H), 3.76 (s, 2H), 4.05 (p, 1H), 4.22 (q, 2H), 6.80 (s, 1H), 7.35 (d,1H), 7.52 (s, 1H), 8.41 (br d, 1H), 11.9 (br s, 1H); HPLC-MS: m/z=424.1(M+23); R_(t)=4.48 min.

Example 469 General Procedure J{2-[3-(2-Cyclobutanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

The title compound (112 mg, 73%) was prepared from{2-[3-(2-cyclobutanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (165 mg, 0.41 mmol) following the general procedure J.

¹H NMR (400 MHz; DMSO d₆): δ 1.70-2.30 (m, 6H), 2.32 (s, 3H), 3.56 (s,2H), 4.19 (brt, 1H), 6.86 (s, 1H), 7.39 (d, 1H), 7.63 (s, 1H), 8.22 (d,1H), 10.81 (s, 1H), 12.15 (br s, 2H); HPLC-MS: m/z=396.1 (M+23);R_(t)=3.75 min.

Example 470 General Procedure AA{2-[3-(2-Cyclohexanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

Crude (2-amino-5-methyl-phenyl)-cyclohexyl-methanone (75%, oil) wasprepared in a similar fashion as described for(2-amino-5-methyl-phenyl)-cyclopropyl-methanone usingcyclohexanecarboxylic acid methoxy-methyl-amide instead ofcyclopropanecarboxylic acid methoxy-methyl-amide.

The title compound (188 mg, 48%) was prepared from crude(2-amino-5-methyl-phenyl)-cyclohexyl-methanone (200 mg, 0.92 mmol) andethyl-2-amino-4-thiazolyl acetate (171 mg, 1.06 mmol) following thegeneral procedure AA.

¹H NMR (400 MHz; CDCl₃): δ 1.30 (t, 3H), 1.37-1.59 (m, 5H), 1.71-1.91(m, 5H), 2.37 (s, 3H), 3.30 (br s, 1H), 3.73 (s, 2H), 4.22 (q, 2H), 6.78(s, 1H), 7.34 (d, 1H), 7.68 (s, 1H), 8.39 (br d, 1H), 11.78 (br s, 1H);HPLC-MS: m/z=452.2 (M+23); R_(t)=4.92 min.

Example 471 General Procedure J{2-[3-(2-Cyclohexanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

The title compound (100 mg, 89%) was prepared from{2-[3-(2-cyclohexanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (112 mg, 0.28 mmol) following the general procedure J.

¹H NMR (400 MHz; DMSO d₆): δ 1.13-1.45 (m, 5H), 1.62-1.83 (m, 5H), 2.34(s, 3H), 3.42 (br s, 1H), 3.57 (s, 2H), 6.83 (s, 1H), 7.39 (d, 1H), 7.81(s, 1H), 8.15 (d, 1H), 10.50 (s, 1H), 12.07 (br s, 2H); HPLC-MS:m/z=402.0 (M+1); R_(t)=4.18 min.

Example 472{2-[(2-Cyclopentanecarbonyl-4-methyl-phenylaminooxalyl)-amino]-thiazol-4-yl}-aceticacid ethyl ester

To a solution of ethyl-2-aminothiazole-4-acetate (2 g) indichloromethane (80 mL) at ice bath temperature was added ethyl oxalylchloride (1.2 mL) and the reaction stirred 1 h. The reaction mixture waswashed with water, and the organic phase concentrated to giveN-(4-ethoxycarbonylmethyl-thiazol-2-yl)-oxalamic acid ethyl ester (1.2g).

To N-(4-ethoxycarbonylmethyl-thiazol-2-yl)-oxalamic acid ethyl ester (1g) was added THF (5 mL) and 2 N lithium hydroxide (4 mL). A whiteprecipitated formed and after 1 h the reaction mixture was acidified topH5 and the white precipitate recovered by filtration, and trituratedwith a 1:1 mixture of ether and ethyl acetate to remove unreactedstarting material. The solid residue was dried in a vacuum oven to giveN-(4-ethoxycarbonylmethyl-thiazol-2-yl)-oxalamic acid (300 mg).

N-(4-ethoxycarbonylmethyl-thiazol-2-yl)-oxalamic acid (80 mg) wasdissolved in DMF (5 mL) and(2-amino-5-methyl-phenyl)-cyclopentyl-methanone was added followed byPyBOP. The reaction was stirred for 24 h and water was added. Theaqueous phase was extracted with ether/ethyl acetate and the organicphase dried, concentrated and purified by flash chromatography to givethe title compound (15 mg).

¹H NMR (CDCl₃): 1.25 (3H, t), 1.6-2.1 (8H, m), 2.45 (3H, s), 3.65-3.75(1H, m), 3.7 (1H, s), 4.2 (4H, q), 6.9 (1H), 7.4 (1H, dd), 7.8 (1H, s),8.65 (1H, d), 10.5 (1H, bs), 13.3 (1H, s).

Example 473{2-[(2-Cyclopentanecarbonyl-4-methyl-phenylaminooxalyl)-amino]-thiazol-4-yl}-aceticacid

To{2-[(2-cyclopentanecarbonyl-4-methyl-phenylaminooxalyl)-amino]-thiazol-4-yl}-aceticacid ethyl ester (15 mg) in methanol (2 mL) was added 1N sodiumhydroxide (1N) and the mixture was stirred 3 h at room temperature. Themixture was acidified with 1N HCl, concentrated under reduced pressureand purified by HPLC to give the title compound (4 mg).

LCMS (m/z): 416 (M+1)

¹H NMR (CDCl₃+MeOD): 1.6-2.1 (8H, m), 2.45 (3H, s), 3.7 (1H, s),3.70-3.85 (1H, m), 6.9 (1H), 7.4 (1H, dd), 7.8 (1H, s), 8.65 (1H, d),13.3 (1H, s).

Example 474[2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-aceticacid ethyl ester

To a solution of{5-chloro-2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (0.1 g, 0.22 mmol) in DMF (4 mL) was added sodiumhydrogen carbonate (0.075 g, 0.89 mmol) and 2-puridylthiole (0.027 g,0.24 mmol). The reaction mixture was stirred under nitrogen in apressure bottle excluded from light for 2.0 hour at 80° C. The crudeproduct was purified by flash chromatography (isopropanole/heptane 1:4)and recrystallized (dichloromethane/heptane) to afford the titlecompound (0.02 g).

¹H NMR (300 MHz, CDCl₃): δ 1.20 (t, 3H), 1.60-1.82 (m, 4H), 1.82-2.02(m, 4H), 2.38 (s, 3H), 3.68-3.80 (m, 1H), 3.85 (s, 2H), 4.12 (q, 2H),7.00 (t, 2H), 7.35 (d, 1H), 7.50 (t, 1H), 7.73 (s, 1H), 8.40 (m, 2H),11.80 (s, 1H).

Example 475 General Procedure (M){2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

To a stirred solution of (4-trifluoromethyl-phenyl)-carbamic acidtert-butyl ester (15 mmol) in Et₂O (40 mL) under a nitrogen atmospherewas added dropwise a 1.7 M solution of t-BuLi in pentan (38 mmol) over a10-min period at −20° C. The mixture was stirred at −15° C. for 1.5 hand then cyclopentanecarboxylic acid methoxy-methyl-amide (20 mmol) wasadded over 5 min. The mixture was allowed to warm to room temperatureand stirred for further 1 h before it was quenched with aqueous NH₄Cl.The organic phase was isolated and the aqueous phase was extracted withCH₂Cl₂, and the combined organic phases were dried and concentrated invacuo. The crude material was dissolved in CH₂Cl₂ (25 mL) and TFA (25mL) and stirred at room temperature for 2 h. The reaction mixture wasevaporated in vacuo, and added aqueous NaHCO3 to pH 7 and extracted withCH₂Cl₂, dried and concentrated to give a crude product which waspurified by flash chromatography (Quad flash 40, EtOAc-Heptane0:1->1:3). This gave 70% of(2-amino-5-trifluoromethyl-phenyl)-cyclopentyl-methanone as an oil.

The title compound (15%) was prepared from(2-amino-5-trifluoromethyl-phenyl)-cyclopentyl-methanone andethyl-2-amino-4-thiazolyl acetate following the general procedure M.

¹H NMR (400 MHz; CDCl₃): δ 1.28 (t, 3H), 1.64-1.99 (m, 8H), 3.70 (brt,1H), 3.74 (s, 2H), 4.20 (q, 2H), 6.74 (s, 1H), 7.73 (d, 1H), 8.13 (s,1H), 8.74 (br s, 1H), 9.53 (br s, 1H), 11.82 (br s, 1H); HPLC-MS:m/z=492.1 (M+23); R_(t)=5.02 min.

Example 476 General Procedure J{2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

The title compound (13 mg, 33%) was prepared from{2-[3-(2-cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (42 mg, 0.09 mmol) following the general procedure J.

¹H NMR (400 MHz; DMSO d₆): δ 1.65-1.95 (m, 8H), 3.60 (s, 2H), 3.99 (brs, 1H), 6.94 (s, 1H), 7.90 (d, 1H), 8.25 (br s, 1H), 8.54 (br s, 1H),10.94 (br s, 1H), 12.25 (br s, 2H); HPLC-MS: m/z=426.1 (M+23);R_(t)=4.49 min.

Example 477 General Procedure (AA){2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

To a stirred solution of (4-chloro-phenyl)-carbamic acid tert-butylester (35 mmol) in Et₂O (80 mL) under a nitrogen atmosphere was addeddropwise a 1.7 M solution of t-BuLi in pentan (88 mmol) over a 10-minperiod at −20° C. The mixture was stirred at 0° C. for 1.5 h and thencyclopentanecarboxylic acid methoxy-methyl-amide (45 mmol) was addedover 5 min. The mixture was allowed to warm to room temperature andstirred for further 1 h before it was quenched with aqueous NH₄Cl. Theorganic phase was isolated and the aqueous phase was extracted withCH₂Cl₂, and the combined organic phases were dried and concentrated invacuo. The crude material was dissolved in CH₂Cl₂ (50 mL) and TFA (50mL) and stirred at room temperature for 1 h. The reaction mixture wasevaporated in vacuo, and added aqueous NaHCO3 to pH 7 and extracted withCH₂Cl₂, dried and concentrated to give a crude product which waspurified by flash chromatography (Quad flash 65, EtOAc-Heptane0:1->1:3). This gave 75% of(2-amino-5-chloro-phenyl)-cyclopentyl-methanone as an oil.

The title compound (30%) was prepared from(2-amino-5-chloro-phenyl)-cyclopentyl-methanone andethyl-2-amino-4-thiazolyl acetate following the general procedure M.

¹H NMR (400 MHz; CDCl₃): δ 1.28 (t, 3H), 1.62-1.99 (m, 8H), 3.3.67 (brt,1H), 3.73 (s, 2H), 4.20 (q, 2H), 6.72 (s, 1H), 7.46 (dd, 1H), 7.84 (d,1H), 8.56 (br s, 1H), 9.50 (br s, 1H), 11.58 (br s, 1H); HPLC-MS:m/z=458.0 (M+23); R_(t)=4.86 min.

Example 478 General Procedure J{2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid

The title compound (39 mg, 85%) was prepared from{2-[3-(4-chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (49 mg, 0.11 mmol) following the general procedure J.

¹H NMR (400 MHz; DMSO d₆): δ 1.67-1.92 (m, 8H), 3.59 (s, 2H), 3.89 (brs, 1H), 6.88 (s, 1H), 7.63 (d, 1H), 8.04 (br s, 1H), 8.32 (br s, 1H),10.64 (s, 1H), 12.20 (br s, 2H); HPLC-MS: m/z=430.0 (M+23); R_(t)=4.11min.

Example 479 General Procedure (M){2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester

To a stirred solution of (4-fluoro-phenyl)-carbamic acid tert-butylester (9.5 mmol) in Et₂O (20 mL) under a nitrogen atmosphere was addeddropwise a 1.7 M solution of t-BuLi in pentan (22 mmol) over a 10-minperiod at −30° C. The mixture was stirred at −20° C. for 1.5 h and thencyclopentanecarboxylic acid methoxy-methyl-amide (10.5 mmol) was addedover 5 min. The mixture was allowed to warm to room temperature andstirred for further 1 h before it was quenched with aqueous NH₄Cl. Theorganic phase was isolated and the aqueous phase was extracted withCH₂Cl₂, and the combined organic phases were dried and concentrated invacuo. The crude material was dissolved in CH₂Cl₂ (25 mL) and TFA (25mL) and stirred at room temperature for 2 h. The reaction mixture wasevaporated in vacuo, and added aqueous NaHCO3 to pH 7 and extracted withCH₂Cl₂, dried and concentrated to give a crude product which waspurified by flash chromatography (Quad flash 40, EtOAc-Heptane0:1->1:3). This gave 60% of(2-amino-5-fluoro-phenyl)-cyclopentyl-methanone as an oil.

The title compound (26%) was prepared from(2-amino-5-fluoro-phenyl)-cyclopentyl-methanone andethyl-2-amino-4-thiazolyl acetate following the general procedure AA.

¹H NMR (400 MHz; CDCl₃): δ 1.28 (t, 3H), 1.63-1.97 (m, 8H), 3.64 (brt,1H), 3.73 (s, 2H), 4.20 (q, 2H), 6.72 (s, 1H), 7.22-7.29 (m, 1H), 7.58(dd, 1H), 8.55 (br s, 1H), 9.40 (br s, 1H), 11.45 (br s, 1H); HPLC-MS:m/z=442.0 (M+23); R_(t)=4.49 min.

Example 480 General Procedure J{2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-thiazol-4-yl}-aceticacid

The title compound (75 mg, 87%) was prepared from{2-[3-(2-cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester (92 mg, 0.22 mmol) following the general procedure J.

¹H NMR (400 MHz; DMSO d₆): δ 1.65-1.94 (m, 8H), 3.57 (s, 2H), 3.84 (brs, 1H), 6.88 (s, 1H), 7.45 (t, 1H), 7.85 (br s, 1H), 8.25 (br s, 1H),10.48 (s, 1H), 12.10 (br s, 2H); HPLC-MS: m/z=414.1 (M+23); R_(t)=3.74min.

Using the methods disclosed herein the following compounds may also bemade:

-   1-(5-Chloro-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea-   1-(5-Chloro-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-phenyl)-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-(5-chloro-thiazol-2-yl)-urea-   1-(5-Chloro-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-fluoro-phenyl)-urea-   1-(5-Chloro-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-urea-   1-(5-Chloro-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-urea-   1-(5-Chloro-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-dimethylamino-phenyl)-urea-   1-(5-Chloro-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-urea-   1-(5-Chloro-thiazol-2-yl)-3-(3-cyclopentanecarbonyl-pyridin-4-yl)-urea-   1-(5-Chloro-thiazol-2-yl)-3-(4-cyclopentanecarbonyl-pyridin-3-yl)-urea-   1-(5-Chloro-thiazol-2-yl)-3-(3-cyclopentanecarbonyl-pyridin-2-yl)-urea-   1-(5-Bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea-   1-(5-Bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-phenyl)-urea-   1-(5-Bromo-thiazol-2-yl)-3-(4-chloro-2-cyclopentanecarbonyl-phenyl)-urea-   1-(5-Bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-fluoro-phenyl)-urea-   1-(5-Bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-urea-   1-(5-Bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-urea-   1-(5-Bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-dimethylamino-phenyl)-urea-   1-(5-Bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-urea-   1-(5-Bromo-thiazol-2-yl)-3-(3-cyclopentanecarbonyl-pyridin-4-yl)-urea-   1-(5-Bromo-thiazol-2-yl)-3-(4-cyclopentanecarbonyl-pyridin-3-yl)-urea-   1-(5-Bromo-thiazol-2-yl)-3-(3-cyclopentanecarbonyl-pyridin-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-methylsulfanyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-(5-methylsulfanyl-thiazol-2-yl)-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-(5-methylsulfanyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-(5-methylsulfanyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-(5-methylsulfanyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-(5-methylsulfanyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-(5-methylsulfanyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-(5-methylsulfanyl-thiazol-2-yl)-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-(5-methylsulfanyl-thiazol-2-yl)-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-(5-methylsulfanyl-thiazol-2-yl)-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-(5-methylsulfanyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-[5-(1H-imidazole-2-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-[5-(1H-imidazole-2-sulfonyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-[5-(1H-imidazole-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-2-yl]-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-2-yl]-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-[5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-[5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-[5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-[5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-[5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-[5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-[5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Chloro-2-[3-(2-cyclopentanecarbonyl-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Chloro-2-[3-(4-chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Chloro-2-[3-(3-cyclopentanecarbonyl-pyridin-4-yl)-ureido]-thiazole-4-carboxylic    acid-   5-Chloro-2-[3-(4-cyclopentanecarbonyl-pyridin-3-yl)-ureido]-thiazole-4-carboxylic    acid-   5-Chloro-2-[3-(3-cyclopentanecarbonyl-pyridin-2-yl)-ureido]-thiazole-4-carboxylic    acid-   5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Bromo-2-[3-(2-cyclopentanecarbonyl-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Bromo-2-[3-(4-chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-thiazole-4-carboxylic    acid-   5-Bromo-2-[3-(3-cyclopentanecarbonyl-pyridin-4-yl)-ureido]-thiazole-4-carboxylic    acid-   5-Bromo-2-[3-(4-cyclopentanecarbonyl-pyridin-3-yl)-ureido]-thiazole-4-carboxylic    acid-   5-Bromo-2-[3-(3-cyclopentanecarbonyl-pyridin-2-yl)-ureido]-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-methylsulfanyl-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-methylsulfanyl-thiazole-4-carboxylic    acid-   2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-methylsulfanyl-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-methylsulfanyl-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-methylsulfanyl-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-methylsulfanyl-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-methylsulfanyl-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-methylsulfanyl-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-methylsulfanyl-thiazole-4-carboxylic    acid-   2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-methylsulfanyl-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-methylsulfanyl-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-methanesulfonyl-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-methanesulfonyl-thiazole-4-carboxylic    acid-   2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-methanesulfonyl-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-methanesulfonyl-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-methanesulfonyl-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-methanesulfonyl-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-methanesulfonyl-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-methanesulfonyl-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-methanesulfonyl-thiazole-4-carboxylic    acid-   2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-methanesulfonyl-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-methanesulfonyl-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(pyridine-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(pyridine-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(pyridine-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazole-4-carboxylic    acid-   {5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Chloro-2-[3-(2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Chloro-2-[3-(4-chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Chloro-2-[3-(3-cyclopentanecarbonyl-pyridin-4-yl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Chloro-2-[3-(4-cyclopentanecarbonyl-pyridin-3-yl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Chloro-2-[3-(3-cyclopentanecarbonyl-pyridin-2-yl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Bromo-2-[3-(2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Bromo-2-[3-(4-chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Bromo-2-[3-(3-cyclopentanecarbonyl-pyridin-4-yl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Bromo-2-[3-(4-cyclopentanecarbonyl-pyridin-3-yl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Bromo-2-[3-(3-cyclopentanecarbonyl-pyridin-2-yl)-ureido]-thiazol-4-yl}-acetic    acid-   {2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   {2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   {2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   {2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   {2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   {2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   {2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   {2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   {2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   {2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   {2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   [2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-yl]-acetic    acid-   1-(5-Chloro-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea-   1-(5-Chloro-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-phenyl)-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-(5-chloro-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(5-Chloro-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-fluoro-phenyl)-urea-   1-(5-Chloro-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-urea-   1-(5-Chloro-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-urea-   1-(5-Chloro-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-dimethylamino-phenyl)-urea-   1-(5-Chloro-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-urea-   1-(5-Chloro-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(3-cyclopentanecarbonyl-pyridin-4-yl)-urea-   1-(5-Chloro-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(4-cyclopentanecarbonyl-pyridin-3-yl)-urea-   1-(5-Chloro-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(3-cyclopentanecarbonyl-pyridin-2-yl)-urea-   1-(5-Bromo-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea-   1-(5-Bromo-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-phenyl)-urea-   1-(5-Bromo-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(4-chloro-2-cyclopentanecarbonyl-phenyl)-urea-   1-(5-Bromo-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-fluoro-phenyl)-urea-   1-(5-Bromo-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-urea-   1-(5-Bromo-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-urea-   1-(5-Bromo-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-dimethylamino-phenyl)-urea-   1-(5-Bromo-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-urea-   1-(5-Bromo-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(3-cyclopentanecarbonyl-pyridin-4-yl)-urea-   1-(5-Bromo-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(4-cyclopentanecarbonyl-pyridin-3-yl)-urea-   1-(5-Bromo-4-phenylsulfanylmethyl-thiazol-2-yl)-3-(3-cyclopentanecarbonyl-pyridin-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-methylsulfanyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-(5-methylsulfanyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-(5-methylsulfanyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-(5-methylsulfanyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-(5-methylsulfanyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-(5-methylsulfanyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-(5-methylsulfanyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-(5-methylsulfanyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-(5-methylsulfanyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-(5-methylsulfanyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-(5-methylsulfanyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-methanesulfonyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-(5-methanesulfonyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-(5-methanesulfonyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-(5-methanesulfonyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-(5-methanesulfonyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-(5-methanesulfonyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-(5-methanesulfonyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-(5-methanesulfonyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-(5-methanesulfonyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-(5-methanesulfonyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-(5-methanesulfonyl-4-phenylsulfanylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-[4-phenylsulfanyl    methyl-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-[4-phenylsulfanylmethyl-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-[4-phenylsulfanylmethyl-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-[4-phenylsulfanylmethyl-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[4-phenylsulfanylmethyl-5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-[4-phenylsulfanylmethyl-5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-[4-phenylsulfanylmethyl-5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-[4-phenylsulfanylmethyl-5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[5-(1H-imidazol-2-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-[5-(1H-imidazol-2-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-[5-(1H-imidazol-2-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-[5-(1H-imidazol-2-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[5-(1H-imidazole-2-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-[5-(1H-imidazole-2-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-[5-(1H-imidazole-2-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-[5-(1H-imidazole-2-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonyl)-4-phenylsulfanylmethyl-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[4-phenylsulfanylmethyl-5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[4-phenylsulfanylmethyl-5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-3-[4-phenylsulfanylmethyl-5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[4-phenylsulfanylmethyl-5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-3-[4-phenylsulfanylmethyl-5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-3-[4-phenylsulfanylmethyl-5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-3-[4-phenylsulfanylmethyl-5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[4-phenylsulfanylmethyl-5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-4-yl)-3-[4-phenylsulfanylmethyl-5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Cyclopentanecarbonyl-pyridin-3-yl)-3-[4-phenylsulfanylmethyl-5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   1-(3-Cyclopentanecarbonyl-pyridin-2-yl)-3-[4-phenylsulfanylmethyl-5-(1H-tetrazole-5-sulfonyl)-thiazol-2-yl]-urea-   N-{5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Chloro-2-[3-(2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Chloro-2-[3-(4-chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Chloro-2-[3-(2-cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Chloro-2-[3-(3-cyclopentanecarbonyl-pyridin-4-yl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Chloro-2-[3-(4-cyclopentanecarbonyl-pyridin-3-yl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Chloro-2-[3-(3-cyclopentanecarbonyl-pyridin-2-yl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Bromo-2-[3-(2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Bromo-2-[3-(4-chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Bromo-2-[3-(2-cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Bromo-2-[3-(3-cyclopentanecarbonyl-pyridin-4-yl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Bromo-2-[3-(4-cyclopentanecarbonyl-pyridin-3-yl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{5-Bromo-2-[3-(3-cyclopentanecarbonyl-pyridin-2-yl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-methylsulfanyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-methylsulfanyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-methylsulfanyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-methylsulfanyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-methanesulfonyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-methanesulfonyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-methanesulfonyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-{2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-methanesulfonyl-thiazol-4-ylmethyl}-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(pyridin-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(pyridine-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1H-imidazole-2-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1-methyl-1H-tetrazol-5-ylsulfanyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1-methyl-1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(4-Chloro-2-cyclopentanecarbonyl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-trifluoromethyl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-methoxy-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-dimethylamino-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(3-Cyclopentanecarbonyl-pyridin-4-yl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(4-Cyclopentanecarbonyl-pyridin-3-yl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-[2-[3-(3-Cyclopentanecarbonyl-pyridin-2-yl)-ureido]-5-(1H-tetrazole-5-sulfonyl)-thiazol-4-ylmethyl]-methanesulfonamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-thiazol-2-yl-oxalamide-   N-(5-bromo-thiazol-2-yl)-N′-(2-cyclopentanecarbonyl-phenyl)-oxalamide-   N-(5-chloro-thiazol-2-yl)-N′-(2-cyclopentanecarbonyl-phenyl)-oxalamide-   4;    N-(2-cyclopentanecarbonyl-phenyl)-N′-(5-methylsulfanyl-thiazol-2-yl)-oxalamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-(5-methanesulfonyl-thiazol-2-yl)-oxalamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   {5-bromo-2-[(2-cyclopentanecarbonyl-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   {5-chloro-2-[(2-cyclopentanecarbonyl-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   {2-[(2-cyclopentanecarbonyl-phenylaminooxalyl)-amino]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[(2-cyclopentanecarbonyl-phenylaminooxalyl)-amino]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   [2-[(2-cyclopentanecarbonyl-phenylaminooxalyl)-amino]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]acetic    acid-   [2-[(2-cyclopentanecarbonyl-phenylaminooxalyl)-amino]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   N-(2-cyclopentanecarbonyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-cyclopentanecarbonyl-phenyl)-oxalamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-cyclopentanecarbonyl-phenyl)-oxalamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-oxalamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-thiazol-2-yl-malonamide-   N-(5-bromo-thiazol-2-yl)-N′-(2-cyclopentanecarbonyl-phenyl)-malonamide-   N-(5-chloro-thiazol-2-yl)-N′-(2-cyclopentanecarbonyl-phenyl)-malonamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-(5-methylsulfanyl-thiazol-2-yl)-malonamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-(5-methanesulfonyl-thiazol-2-yl)-malonamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   {2-[2-(2-cyclopentanecarbonyl-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {5-bromo-2-[2-(2-cyclopentanecarbonyl-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {5-chloro-2-[2-(2-cyclopentanecarbonyl-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {2-[2-(2-cyclopentanecarbonyl-phenylcarbamoyl)-acetylamino]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[2-(2-cyclopentanecarbonyl-phenylcarbamoyl)-acetylamino]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   [2-[2-(2-cyclopentanecarbonyl-phenylcarbamoyl)-acetylamino]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[2-(2-cyclopentanecarbonyl-phenylcarbamoyl)-acetylamino]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   N-(2-cyclopentanecarbonyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-cyclopentanecarbonyl-phenyl)-malonamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-cyclopentanecarbonyl-phenyl)-malonamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-malonamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   N-(2-cyclopentanecarbonyl-phenyl)-N′-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-(2-isobutoxy-phenyl)-N′-thiazol-2-yl-oxalamide-   N-(5-bromo-thiazol-2-yl)-N′-(2-isobutoxy-phenyl)-oxalamide-   N-(5-chloro-thiazol-2-yl)-N′-(2-isobutoxy-phenyl)-oxalamide-   N-(2-isobutoxy-phenyl)-N′-(5-methylsulfanyl-thiazol-2-yl)-oxalamide-   N-(2-isobutoxy-phenyl)-N′-(5-methanesulfonyl-thiazol-2-yl)-oxalamide-   N-(2-isobutoxy-phenyl)-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   N-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-N′-(2-isobutoxy-phenyl)-oxalamide-   {2-[(2-isobutoxy-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic acid-   {5-bromo-2-[(2-isobutoxy-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   {5-chloro-2-[(2-isobutoxy-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   {2-[(2-isobutoxy-phenylaminooxalyl)-amino]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[(2-isobutoxy-phenylaminooxalyl)-amino]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   [2-[(2-isobutoxy-phenylaminooxalyl)-amino]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   {5-(1H-imidazol-2-ylsulfanyl)-2-[(2-isobutoxy-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   N-(2-isobutoxy-phenyl)-N′-[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-isobutoxy-phenyl)-oxalamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-isobutoxy-phenyl)-oxalamide-   N-(2-isobutoxy-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-oxalamide-   N-(2-isobutoxy-phenyl)-N′-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-(2-isobutoxy-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   N-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-isobutoxy-phenyl)-oxalamide-   N-(2-isobutoxy-phenyl)-N′-thiazol-2-yl-malonamide-   N-(5-bromo-thiazol-2-yl)-N′-(2-isobutoxy-phenyl)-malonamide-   N-(5-chloro-thiazol-2-yl)-N′-(2-isobutoxy-phenyl)-malonamide-   N-(2-isobutoxy-phenyl)-N′-(5-methylsulfanyl-thiazol-2-yl)-malonamide-   N-(2-isobutoxy-phenyl)-N′-(5-methanesulfonyl-thiazol-2-yl)-malonamide-   N-(2-isobutoxy-phenyl)-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   N-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-N′-(2-isobutoxy-phenyl)-malonamide-   {2-[2-(2-isobutoxy-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {5-bromo-2-[2-(2-isobutoxy-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {5-chloro-2-[2-(2-isobutoxy-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {2-[2-(2-isobutoxy-phenylcarbamoyl)-acetylamino]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[2-(2-isobutoxy-phenylcarbamoyl)-acetylamino]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   [2-[2-(2-isobutoxy-phenylcarbamoyl)-acetylamino]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   {5-(1H-imidazol-2-ylsulfanyl)-2-[2-(2-isobutoxy-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   N-(2-isobutoxy-phenyl)-N′-[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-isobutoxy-phenyl)-malonamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-isobutoxy-phenyl)-malonamide-   N-(2-isobutoxy-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-malonamide-   N-(2-isobutoxy-phenyl)-N′-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-(2-isobutoxy-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   N-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-isobutoxy-phenyl)-malonamide-   N-[2-(2-methoxy-phenoxy)-phenyl]-N′-thiazol-2-yl-oxalamide-   N-(5-bromo-thiazol-2-yl)-N′-[2-(2-methoxy-phenoxy)-phenyl]-oxalamide-   N-(5-chloro-thiazol-2-yl)-N′-[2-(2-methoxy-phenoxy)-phenyl]-oxalamide-   N-[2-(2-methoxy-phenoxy)-phenyl]-N′-(5-methylsulfanyl-thiazol-2-yl)-oxalamide-   N-(5-methanesulfonyl-thiazol-2-yl)-N′-[2-(2-methoxy-phenoxy)-phenyl]-oxalamide-   N-[2-(2-methoxy-phenoxy)-phenyl]-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   N-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-oxalamide-   (2-{[2-(2-methoxy-phenoxy)-phenylaminooxalyl]-amino}-thiazol-4-yl)-acetic    acid-   (5-bromo-2-{[2-(2-methoxy-phenoxy)-phenylaminooxalyl]-amino}-thiazol-4-yl)-acetic    acid-   (5-chloro-2-{[2-(2-methoxy-phenoxy)-phenylaminooxalyl]-amino}-thiazol-4-yl)-acetic    acid-   (2-{[2-(2-methoxy-phenoxy)-phenylaminooxalyl]-amino}-5-methylsulfanyl-thiazol-4-yl)-acetic    acid-   (5-methanesulfonyl-2-{[2-(2-methoxy-phenoxy)-phenylaminooxalyl]-amino}-thiazol-4-yl)-acetic    acid-   [2-{[2-(2-methoxy-phenoxy)-phenylaminooxalyl]-amino}-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   (5-(1H-imidazol-2-ylsulfanyl)-2-{[2-(2-methoxy-phenoxy)-phenylaminooxalyl]-amino}-thiazol-4-yl)-acetic    acid-   N-[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-oxalamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-oxalamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-oxalamide-   N-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-oxalamide-   N-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-oxalamide.-   N-[4-(methanesulfonylamino-methyl)-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-oxalamide-   N-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-oxalamide-   N-[2-(2-methoxy-phenoxy)-phenyl]-N′-thiazol-2-yl-malonamide-   N-(5-bromo-thiazol-2-yl)-N′-[2-(2-methoxy-phenoxy)-phenyl]-malonamide-   N-(5-chloro-thiazol-2-yl)-N′-[2-(2-methoxy-phenoxy)-phenyl]-malonamide-   N-[2-(2-methoxy-phenoxy)-phenyl]-N′-(5-methylsulfanyl-thiazol-2-yl)-malonamide-   N-(5-methanesulfonyl-thiazol-2-yl)-N′-[2-(2-methoxy-phenoxy)-phenyl]-malonamide-   N-[2-(2-methoxy-phenoxy)-phenyl]-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   N-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-malonamide-   (2-{2-[2-(2-methoxy-phenoxy)-phenylcarbamoyl]-acetylamino}-thiazol-4-yl)-acetic    acid-   (5-bromo-2-{2-[2-(2-methoxy-phenoxy)-phenylcarbamoyl]-acetylamino}-thiazol-4-yl)-acetic    acid-   (5-chloro-2-{2-[2-(2-methoxy-phenoxy)-phenylcarbamoyl]-acetylamino}-thiazol-4-yl)-acetic    acid-   (2-{2-[2-(2-methoxy-phenoxy)-phenylcarbamoyl]-acetylamino}-5-methylsulfanyl-thiazol-4-yl)-acetic    acid-   (5-methanesulfonyl-2-{2-[2-(2-methoxy-phenoxy)-phenylcarbamoyl]-acetylamino}-thiazol-4-yl)-acetic    acid-   [2-{2-[2-(2-methoxy-phenoxy)-phenylcarbamoyl]-acetylamino}-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   (5-(1H-imidazol-2-ylsulfanyl)-2-{2-[2-(2-methoxy-phenoxy)-phenylcarbamoyl]-acetylamino}-thiazol-4-yl)-acetic    acid-   N[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-malonamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-malonamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-malonamide-   N-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-malonamide-   N-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-malonamide-   N-[4-(methanesulfonylamino-methyl)-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-malonamide-   N-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[2-(2-methoxy-phenoxy)-phenyl]-malonamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-thiazol-2-yl-oxalamide-   N-(5-bromo-thiazol-2-yl)-N′-(2-cyclopentanecarbonyl-4-methyl-phenyl)-oxalamide-   N-(5-chloro-thiazol-2-yl)-N′-(2-cyclopentanecarbonyl-4-methyl-phenyl)-oxalamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-(5-methylsulfanyl-thiazol-2-yl)-oxalamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-(5-methanesulfonyl-thiazol-2-yd)-oxalamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   {2-[(2-cyclopentanecarbonyl-4-methyl-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   {5-bromo-2-[(2-cyclopentanecarbonyl-4-methyl-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   {5-chloro-2-[(2-cyclopentanecarbonyl-4-methyl-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   {2-[(2-cyclopentanecarbonyl-4-methyl-phenylaminooxalyl)-amino]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[(2-cyclopentanecarbonyl-4-methyl-phenylaminooxalyl)-amino]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   [2-[(2-cyclopentanecarbonyl-4-methyl-phenylaminooxalyl)-amino]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[(2-cyclopentanecarbonyl-4-methyl-phenylaminooxalyl)-amino]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-cyclopentanecarbonyl-4-methyl-phenyl)-oxalamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-cyclopentanecarbonyl-4-methyl-phenyl)-oxalamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-oxalamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-thiazol-2-yl-malonamide-   N-(5-bromo-thiazol-2-yl)-N′-(2-cyclopentanecarbonyl-4-methyl-phenyl)-malonamide-   N-(5-chloro-thiazol-2-yl)-N′-(2-cyclopentanecarbonyl-4-methyl-phenyl)-malonamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-(5-methylsulfanyl-thiazol-2-yl)-malonamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-(5-methanesulfonyl-thiazol-2-yl)-malonamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   {2-[2-(2-cyclopentanecarbonyl-4-methyl-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {5-bromo-2-[2-(2-cyclopentanecarbonyl-4-methyl-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {5-chloro-2-[2-(2-cyclopentanecarbonyl-4-methyl-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {2-[2-(2-cyclopentanecarbonyl-4-methyl-phenylcarbamoyl)-acetylamino]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[2-(2-cyclopentanecarbonyl-4-methyl-phenylcarbamoyl)-acetylamino]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   [2-[2-(2-cyclopentanecarbonyl-4-methyl-phenylcarbamoyl)-acetylamino]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[2-(2-cyclopentanecarbonyl-4-methyl-phenylcarbamoyl)-acetylamino]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-cyclopentanecarbonyl-4-methyl-phenyl)-malonamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-cyclopentanecarbonyl-4-methyl-phenyl)-malonamide-   165;165;N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-malonamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   N-(2-cyclopentanecarbonyl-4-methyl-phenyl)-N′-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-(2-isobutoxy-4-methyl-phenyl)-N′-thiazol-2-yl-oxalamide-   N-(5-bromo-thiazol-2-yl)-N′-(2-isobutoxy-4-methyl-phenyl)-oxalamide-   N-(5-chloro-thiazol-2-yl)-N′-(2-isobutoxy-4-methyl-phenyl)-oxalamide-   N-(2-isobutoxy-4-methyl-phenyl)-N′-(5-methylsulfanyl-thiazol-2-yl)-oxalamide-   N-(2-isobutoxy-4-methyl-phenyl)-N′-(5-methanesulfonyl-thiazol-2-yl)-oxalamide-   N-(2-isobutoxy-4-methyl-phenyl)-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   N-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-N′-(2-isobutoxy-4-methyl-phenyl)-oxalamide-   2-[(2-isobutoxy-4-methyl-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   5-bromo-2-[(2-isobutoxy-4-methyl-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   5-chloro-2-[(2-isobutoxy-4-methyl-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   {2-[(2-isobutoxy-4-methyl-phenylaminooxalyl)-amino]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[(2-isobutoxy-4-methyl-phenylaminooxalyl)-amino]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   [2-[(2-isobutoxy-4-methyl-phenylaminooxalyl)-amino]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   {5-(1H-imidazol-2-ylsulfanyl)-2-[(2-isobutoxy-4-methyl-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   N-(2-isobutoxy-4-methyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-isobutoxy-4-methyl-phenyl)-oxalamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-isobutoxy-4-methyl-phenyl)-oxalamide-   N-(2-isobutoxy-4-methyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-oxalamide-   N-(2-isobutoxy-4-methyl-phenyl)-N′-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-(2-isobutoxy-4-methyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   N-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-isobutoxy-4-methyl-phenyl)-oxalamide-   N-(2-isobutoxy-4-methyl-phenyl)-N′-thiazol-2-yl-malonamide-   N-(5-bromo-thiazol-2-yl)-N′-(2-isobutoxy-4-methyl-phenyl)-malonamide-   N-(5-chloro-thiazol-2-yl)-N′-(2-isobutoxy-4-methyl-phenyl)-malonamide-   N-(2-isobutoxy-4-methyl-phenyl)-N′-(5-methylsulfanyl-thiazol-2-yl)-malonamide-   N-(2-isobutoxy-4-methyl-phenyl)-N′-(5-methanesulfonyl-thiazol-2-yl)-malonamide-   N-(2-isobutoxy-4-methyl-phenyl)-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   N-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-N′-(2-isobutoxy-4-methyl-phenyl)-malonamide-   {2-[2-(2-isobutoxy-4-methyl-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {5-bromo-2-[2-(2-isobutoxy-4-methyl-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {5-chloro-2-[2-(2-isobutoxy-4-methyl-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {2-[2-(2-isobutoxy-4-methyl-phenylcarbamoyl)-acetylamino]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[2-(2-isobutoxy-4-methyl-phenylcarbamoyl)-acetylamino]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   [2-[2-(2-isobutoxy-4-methyl-phenylcarbamoyl)-acetylamino]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   {5-(1H-imidazol-2-ylsulfanyl)-2-[2-(2-isobutoxy-4-methyl-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   N-(2-isobutoxy-4-methyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-isobutoxy-4-methyl-phenyl)-malonamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-isobutoxy-4-methyl-phenyl)-malonamide-   N-(2-isobutoxy-4-methyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-malonamide-   N-(2-isobutoxy-4-methyl-phenyl)-N′-[5-methanesulfonyl-4-(methanesulfonyamino-methyl)-thiazol-2-yl]-malonamide-   N-(2-isobutoxy-4-methyl-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   N-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-isobutoxy-4-methyl-phenyl)-malonamide-   N-[2-(2-methoxy-phenoxy)-4-methyl-phenyl]-N′-thiazol-2-yl-oxalamide-   N-(5-bromo-thiazol-2-yl)-N′-[2-(2-methoxy-phenoxy)-4-methyl-phenyl]-oxalamide-   N-(5-chloro-thiazol-2-yl)-N′-[2-(2-methoxy-phenoxy)-4-methyl-phenyl]-oxalamide-   N—[N-(5-methanesulfonyl-thiazol-N—[N-[5-(1H-imidazol-((5-bromo-(5-chloro-((5-methanesulfonyl-[(5-(1H-imidazol-N-[4-(methanesulfonylamino-methyl)-thiazol-N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-N-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-N-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-N-[4-(methanesulfonylamino-methyl)-5-(pyridin-N-[5-(1H-imidazol-N—[N-(5-bromo-thiazol-N-(5-chloro-thiazol-N—[N-(5-methanesulfonyl-thiazol-N—[N-[5-(1H-imidazol-((5-bromo-(5-chloro-((5-methanesulfonyl-[(5-(1H-imidazol-N-[4-(methanesulfonylamino-methyl)-thiazol-N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-N-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-N-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-N-[4-(methanesulfonylamino-methyl)-5-(pyridin-N-[5-(1H-imidazol-N—(N-(5-bromo-thiazol-N-(5-chloro-thiazol-N—(N—(N—(N-({{5-bromo-{5-chloro-{{[[N—(N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-N—(N—(N—(N—(N—(N-(5-bromo-thiazol-N-(5-chloro-thiazol-N—(N—(N—(N-({{5-bromo-5-chloro-{{[[N-(N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-N—(N—(N—(N—(N-(4-fluoro-N-(5-bromo-thiazol-N-(5-chloro-thiazol-N-(4-fluoro-N-(4-fluoro-2-isobutoxy-phenyl)-N′-(5-methanesulfonyl-thiazol-2-yl)-oxalamide    N-(4-fluoro-2-isobutoxy-phenyl)-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-oxalamide    N-(4-fluoro-2-isobutoxy-phenyl)-N′-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   {2-[(4-fluoro-2-isobutoxy-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   {5-bromo-2-[(4-fluoro-2-isobutoxy-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   {5-chloro-2-[(4-fluoro-2-isobutoxy-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   {2-[(4-fluoro-2-isobutoxy-phenylaminooxalyl)-amino]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[(4-fluoro-2-isobutoxy-phenylaminooxalyl)-amino]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   [2-[(4-fluoro-2-isobutoxy-phenylaminooxalyl)-amino]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[(4-fluoro-2-isobutoxy-phenylaminooxalyl)-amino]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(4-fluoro-2-isobutoxy-phenyl)-oxalamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(4-fluoro-2-isobutoxy-phenyl)-oxalamide-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-oxalamide-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-thiazol-2-yl-malonamide-   N-(5-bromo-thiazol-2-yl)-N′-(4-fluoro-2-isobutoxy-phenyl)-malonamide-   N-(5-chloro-thiazol-2-yl)-N′-(4-fluoro-2-isobutoxy-phenyl)-malonamide-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-(5-methylsulfanyl-thiazol-2-yl)-malonamide-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-(5-methanesulfonyl-thiazol-2-yl)-malonamide-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   {2-[2-(4-fluoro-2-isobutoxy-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {5-bromo-2-[2-(4-fluoro-2-isobutoxy-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {5-chloro-2-[2-(4-fluoro-2-isobutoxy-phenylcarbamoyl)-acetylamino]-thiazol-4-yl}-acetic    acid-   {2-[2-(4-fluoro-2-isobutoxy-phenylcarbamoyl)-acetylamino]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid-   {2-[2-(4-fluoro-2-isobutoxy-phenylcarbamoyl)-acetylamino]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   [2-[2-(4-fluoro-2-isobutoxy-phenylcarbamoyl)-acetylamino]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[2-(4-fluoro-2-isobutoxy-phenylcarbamoyl)-acetylamino]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(4-fluoro-2-isobutoxy-phenyl)-malonamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(4-fluoro-2-isobutoxy-phenyl)-malonamide-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-malonamide-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   N-(4-fluoro-2-isobutoxy-phenyl)-N′-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-thiazol-2-yl-oxalamide-   N-(5-bromo-thiazol-2-yl)-N′-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-oxalamide-   N-(5-chloro-thiazol-2-yl)-N′-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-oxalamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-(5-methylsulfanyl-thiazol-2-yl)-oxalamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-(5-methanesulfonyl-thiazol-2-yl)-oxalamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   (2-{[4-fluoro-2-(2-methoxy-phenoxy)-phenylaminooxalyl]-amino}-thiazol-4-yl)-acetic    acid-   (5-bromo-2-{[4-fluoro-2-(2-methoxy-phenoxy)-phenylaminooxalyl]-amino}-thiazol-4-yl)-acetic    acid-   (5-chloro-2-{[4-fluoro-2-(2-methoxy-phenoxy)-phenylaminooxalyl]-amino}-thiazol-4-yl)-acetic    acid-   (2-{[4-fluoro-2-(2-methoxy-phenoxy)-phenylaminooxalyl]-amino}-5-methylsulfanyl-thiazol-4-yl)-acetic    acid-   (2-{[4-fluoro-2-(2-methoxy-phenoxy)-phenylaminooxalyl]-amino}-5-methanesulfonyl-thiazol-4-yl)-acetic    acid-   [2-{[4-fluoro-2-(2-methoxy-phenoxy)-phenylaminooxalyl]-amino}-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-{[4-fluoro-2-(2-methoxy-phenoxy)-phenylaminooxalyl]-amino}-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-oxalamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-oxalamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-oxalamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-[4-(methanesulfonylamino-methyl)-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-thiazol-2-yl-malonamide-   N-(5-bromo-thiazol-2-yl)-N′-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-malonamide-   N-(5-chloro-thiazol-2-yl)-N′-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-malonamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-(5-methylsulfanyl-thiazol-2-yl)-malonamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-(5-methanesulfonyl-thiazol-2-yl)-malonamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   (2-{2-[4-fluoro-2-(2-methoxy-phenoxy)-phenylcarbamoyl]-acetylamino}-thiazol-4-yl)-acetic    acid-   (5-bromo-2-{2-[4-fluoro-2-(2-methoxy-phenoxy)-phenylcarbamoyl]-acetylamino}-thiazol-4-yl)-acetic    acid-   (5-chloro-2-{2-[4-fluoro-2-(2-methoxy-phenoxy)-phenylcarbamoyl]-acetylamino}-thiazol-4-yl)-acetic    acid-   (2-{2-[4-fluoro-2-(2-methoxy-phenoxy)-phenylcarbamoyl]-acetylamino}-5-methylsulfanyl-thiazol-4-yl)-acetic    acid-   (2-{2-[4-fluoro-2-(2-methoxy-phenoxy)-phenylcarbamoyl]-acetylamino}-5-methanesulfonyl-thiazol-4-yl)-acetic    acid-   [2-{2-[4-fluoro-2-(2-methoxy-phenoxy)-phenylcarbamoyl]-acetylamino}-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-{2-[4-fluoro-2-(2-methoxy-phenoxy)-phenylcarbamoyl]-acetylamino}-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-malonamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-malonamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-malonamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-[4-(methanesulfonylamino-methyl)-5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-malonamide-   N-[4-fluoro-2-(2-methoxy-phenoxy)-phenyl]-N′-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-malonamide-   N-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-N′-thiazol-2-yl-oxalamide-   N-(5-bromo-thiazol-2-yl)-N′-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-oxalamide-   N-(5-chloro-thiazol-2-yl)-N′-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-oxalamide-   N-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-N′-(5-methylsulfanyl-thiazol-2-yl)-oxalamide-   N-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-N′-(5-methanesulfonyl-thiazol-2-yl)-oxalamide-   N-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-N′-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   N-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-N′-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-oxalamide-   {2-[(2-cyclopentanecarbonyl-4-methoxy-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   {5-bromo-2-[(2-cyclopentanecarbonyl-4-methoxy-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   {5-chloro-2-[(2-cyclopentanecarbonyl-4-methoxy-phenylaminooxalyl)-amino]-thiazol-4-yl}-acetic    acid-   {2-[(2-cyclopentanecarbonyl-4-methoxy-phenylaminooxalyl)-amino]-5-methylsulfanyl-thiazol-4-yl}-acetic    acid.-   {2-[(2-cyclopentanecarbonyl-4-methoxy-phenylaminooxalyl)-amino]-5-methanesulfonyl-thiazol-4-yl}-acetic    acid-   [2-[(2-cyclopentanecarbonyl-4-methoxy-phenylaminooxalyl)-amino]-5-(pyridin-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   [2-[(2-cyclopentanecarbonyl-4-methoxy-phenylaminooxalyl)-amino]-5-(1H-imidazol-2-ylsulfanyl)-thiazol-4-yl]-acetic    acid-   N-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-N′-[4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-[5-bromo-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-oxalamide-   N-[5-chloro-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-oxalamide-   N-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-N′-[4-(methanesulfonylamino-methyl)-5-methylsulfanyl-thiazol-2-yl]-oxalamide-   N-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-N′-[5-methanesulfonyl-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-oxalamide-   N-(2-cyclopentanecarbonyl-4-methoxy-phenyl)-N′-[N-(2-cyclopentanecarbonyl-N—(N—[N-[4-(methanesulfonylamino-methyl)-N—[N-[4-(methanesulfonylamino-methyl)-N-[5-(1H-imidazol-2-ylsulfanyl)-4-(methanesulfonylamino-methyl)-thiazol-2-yl]-N′-[4-methoxy-2-(2-methoxy-phenoxy)-phenyl]-malonamide-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-morpholin-4-ylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-dimethylaminomethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-piperazin-1-ylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(4-methyl-piperazin-1-ylmethyl)-thiazol-2-yl]-urea-   1-[5-(4-Acetyl-piperazin-1-ylmethyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-thiazol-2-yl]-urea-   (4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-piperazin-1-yl)-acetic    acid-   2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-1H-imidazole-4-carboxylic    acid-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1H-imidazol-2-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1-methyl-1H-imidazol-2-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(4H-[1,2,4]triazol-3-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-thiazol-2-yl]-urea-   (5-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-tetrazol-1-yl)-acetic    acid-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-thiazol-2-yl}-urea-   (5-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-tetrazol-1-yl)-acetic    acid-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[1-(2-dimethylamino-ethyl)-1H-tetrazole-5-sulfonylmethyl]-thiazol-2-yl}-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(4H-[1,2,4]triazole-3-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4]triazole-3-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1-methyl-1H-imidazole-2-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1H-imidazole-2-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridin-2-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridin-3-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridine-3-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridin-4-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridine-4-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridin-4-yloxymethyl)-thiazo-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridin-3-yloxymethyl)-thiazo-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridin-2-yloxymethyl)-thiazol-2-yl]-urea-   (4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethoxy}-phenyl)-acetic    acid-   (4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-phenyl)-acetic    acid-   (4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-phenyl)-acetic    acid-   3-(4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethoxy}-phenyl)-propionic    acid-   3-(4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-phenyl)-propionic    acid-   3-(4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-phenyl)-propionic    acid-   4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-benzoic    acid-   4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-benzoic    acid-   4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethoxy}-benzoic    acid-   N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-acetamide-   N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-methanesulfonamide-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(pyridin-2-ylaminomethyl)-thiazol-2-yl]-urea-   2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-1H-imidazole-4-carboxylic    acid-   2-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-1H-imidazole-4-carboxylic    acid-   2-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-oxazole-4-carboxylic    acid-   2-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-1-methyl-1H-imidazole-4-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-carboxylic    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-carboxylic    acid amide-   2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-carboxylic    acid methylamide-   ({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-acetic    acid-   ({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-methanesulfonyl-amino)-acetic    acid-   N-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-methanesulfonamide-   {2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-acetic    acid-   2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-acetamide-   2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-N-methyl-acetamide-   (2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-acetylamino)-acetic    acid-   N-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-acetyl)-methanesulfonamide-   N-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-methanesulfonamide-   N-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-acetamide-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-guanidinomethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-ureidomethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[3-(2-dimethylamino-ethyl)-ureidomethyl]-thiazol-2-yl}-urea-   {2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-carbamic    acid 2-dimethylamino-ethyl ester-   {2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-carbamic    acid methyl ester-   (2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-carbamic    acid methyl ester-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(2-guanidino-ethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(2-ureido-ethyl)-thiazol-2-yl]-urea-   [3-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-ureido]-acetic    acid-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-{2-[3-(2-dimethylamino-ethyl)-ureido]-ethyl}-thiazol-2-yl)-urea-   (2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-carbamic    acid 2-dimethylamino-ethyl ester-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[2-(1H-imidazol-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[2-(1H-imidazole-2-sulfonyl)-ethyl]-thiazol-2-yl}-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[2-(1-methyl-1H-imidazol-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[2-(1-methyl-1H-imidazole-2-sulfonyl)-ethyl]-thiazol-2-yl}-urea-   2-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethylsulfanyl)-1H-imidazole-4-carboxylic    acid-   6-(2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl)-nicotinic    acid-   6-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-nicotinic    acid-   2-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethylsulfanyl)-1-methyl-1H-imidazole-4-carboxylic    acid-   [4-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethylsulfanyl)-phenyl]-acetic    acid-   [4-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethanesulfonyl)-phenyl]-acetic    acid-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[2-(pyridin-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-[2-(pyridine-2-sulfonyl)-ethyl]-thiazol-2-yl)-urea-   6-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethylsulfanyl)-nicotinic    acid-   6-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethanesulfonyl)-nicotinic    acid-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-[1,2,4]oxadiazol-5-ylmethyl-thiazol-2-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(2-[1,2,4]oxadiazol-5-yl-ethyl)-thiazol-2-yl]-urea-   4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-butyric    acid-   1-(2-Isobutoxy-4-methyl-phenyl)-3-(5-piperidin-1-ylmethyl-thiazol-2-yl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-(5-morpholin-4-ylmethyl-thiazol-2-yl)-urea-   1-(5-Dimethylaminomethyl-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-(5-piperazin-1-ylmethyl-thiazol-2-yl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(4-methyl-piperazin-1-ylmethyl)-thiazol-2-yl]-urea-   1-[5-(4-Acetyl-piperazin-1-ylmethyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-thiazol-2-yl]-urea-   (4-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-piperazin-1-yl)-acetic    acid-   2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-1H-imidazole-4-carboxylic    acid-   1-[5-(1H-Imidazol-2-ylsulfanylmethyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(1-methyl-1H-imidazol-2-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(4H-[1,2,4]triazol-3-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-thiazol-2-yl]-urea-   (5-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-tetrazol-1-yl)-acetic    acid-   1-{5-[1-(2-Dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-thiazol-2-yl}-3-(2-isobutoxy-4-methyl-phenyl)-urea-   (5-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-tetrazol-1-yl)-acetic    acid-   1-{5-[1-(2-Dimethylamino-ethyl)-1H-tetrazole-5-sulfonylmethyl]-thiazol-2-yl}-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(4H-[1,2,4]triazole-3-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4]triazole-3-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(1-methyl-1H-imidazole-2-sulfonylmethyl)-thiazol-2-yl]-urea-   1-[5-(1H-Imidazole-2-sulfonylmethyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-2-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-2-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-3-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-3-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-4-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-4-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-4-yloxymethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-3-yloxymethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-2-yloxymethyl)-thiazol-2-yl]-urea-   (4-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethoxy}-phenyl)-acetic    acid-   (4-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-phenyl)-acetic    acid-   (4-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-phenyl)-acetic    acid-   3-(4-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethoxy}-phenyl)-propionic    acid-   3-(4-{2-[3-(2-isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-phenyl)-propionic    acid-   3-(4-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-phenyl)-propionic    acid-   4-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-benzoic    acid-   4-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-benzoic    acid-   4-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethoxy}-benzoic    acid-   N-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-acetamide-   N-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-methanesulfonamide-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-2-ylaminomethyl)-thiazol-2-yl]-urea-   2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-1H-imidazole-4-carboxylic    acid-   2-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-1H-imidazole-4-carboxylic    acid-   2-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-oxazole-4-carboxylic    acid-   2-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-1-methyl-1H-imidazole-4-carboxylic    acid-   2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-carboxylic    acid-   2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-carboxylic    acid amide-   2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-carboxylic    acid methylamide-   ({2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-acetic    acid-   ({2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-4-thiazole-5-carbonyl}-methanesulfonyl-amino)-acetic    acid-   N-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-methanesulfonamide-   {2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-acetic    acid-   2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-acetamide-   2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-N-methyl-acetamide-   (2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-acetylamino)-acetic    acid-   N-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-acetyl)-methanesulfonamide-   N-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-methanesulfonamide-   N-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-acetamide-   1-(5-Guanidinomethyl-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-(5-ureidomethyl-thiazol-2-yl)-urea-   1-{5-[3-(2-Dimethylamino-ethyl)-ureidomethyl]-thiazol-2-yl}-3-(2-isobutoxy-4-methyl-phenyl)-urea-   {2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-carbamic    acid 2-dimethylamino-ethyl ester-   {2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-carbamic    acid methyl ester-   (2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-carbamic    acid methyl ester-   1-[5-(2-Guanidino-ethyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(2-ureido-ethyl)-thiazol-2-yl]-urea-   [3-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-ureido]-acetic    acid-   1-(5-{2-[3-(2-Dimethylamino-ethyl)-ureido]-ethyl}-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea-   (2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-carbamic    acid 2-dimethylamino-ethyl ester-   1-{5-[2-(1H-Imidazol-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-{5-[2-(1H-Imidazole-2-sulfonyl)-ethyl]-thiazol-2-yl}-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-{5-[2-(1-methyl-1H-imidazol-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-{5-[2-(1-methyl-1H-imidazole-2-sulfonyl)-ethyl]-thiazol-2-yl}-urea-   2-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethylsulfanyl)-1H-imidazole-4-carboxylic    acid-   6-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-nicotinic    acid-   6-{2-[3-(2-Isobutoxy-4-methylphenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-nicotinic    acid-   2-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethylsulfanyl)-1-methyl-1H-imidazole-4-carboxylic    acid-   [4-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethylsulfanyl)-phenyl]-acetic    acid-   [4-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethanesulfonyl)-phenyl]-acetic    acid-   1-(2-Isobutoxy-4-methyl-phenyl)-3-{5-[2-(pyridin-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-{5-[2-(pyridine-2-sulfonyl)-ethyl]-thiazol-2-yl}-urea-   6-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethylsulfanyl)-nicotinic    acid-   6-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethanesulfonyl)-nicotinic    acid-   1-(2-Isobutoxy-4-methyl-phenyl)-3-(5-[1,2,4]oxadiazol-5-ylmethyl-thiazol-2-yl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(2-[1,2,4]oxadiazol-5-yl-ethyl)-thiazol-2-yl]-urea-   4-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-butyric    acid-   1-[5-(1H-Imidazol-2-ylsulfanyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(1-methyl-1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea-   2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-1-methyl-1H-imidazole-4-carboxylic    acid-   2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-sulfonyl}-1-methyl-1H-imidazole-4-carboxylic    acid-   2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-sulfonyl}-1H-imidazole-4-carboxylic    acid-   1-[5-(1H-imidazole-2-sulfonyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-3-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-4-sulfonyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-4-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-3-ylsulfanyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   6-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-nicotinic    acid-   6-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-sulfonyl}-nicotinic    acid-   1-(2-Isobutoxy-4-methyl-phenyl)-3-(5-methanesulfonyl-thiazol-2-yl)-urea-   3-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-sulfonyl}-propionic    acid-   3-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-propionic    acid-   1-(5-Bromo-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea-   {5-Chloro-2-[3-(2-isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Bromo-2-[3-(2-isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-(5-piperidin-1-ylmethyl-thiazol-2-yl)-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-(5-morpholin-4-ylmethyl-thiazol-2-yl)-urea-   1-(5-Dimethylaminomethyl-thiazol-2-yl)-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-(5-piperazin-1-ylmethyl-thiazol-2-yl)-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(4-methyl-piperazin-1-ylmethyl)-thiazol-2-yl]-urea-   1-[5-(4-Acetyl-piperazin-1-ylmethyl)-thiazol-2-yl]-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[5-(4-Methanesulfonyl-piperazin-1-ylmethyl)-thiazol-2-yl]-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   [4-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethyl)-piperazin-1-yl]-acetic    acid-   2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethylsulfanyl)-1H-imidazole-4-carboxylic    acid-   1-[5-(1H-Imidazol-2-ylsulfanylmethyl)-thiazol-2-yl]-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(1-methyl-1H-imidazol-2-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(4H-[1,2,4]triazol-3-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-thiazol-2-yl]-urea-   [5-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethylsulfanyl)-tetrazol-1-yl]-acetic    acid-   1-{5-[1-(2-Dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-thiazol-2-yl}-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   [5-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethanesulfonyl)-tetrazol-1-yl]-acetic    acid-   1-{5-[1-(2-Dimethylamino-ethyl)-1H-tetrazole-5-sulfonylmethyl]-thiazol-2-yl}-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(1-methyl-1H-tetrazole-5-sulfonylmethyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(4H-[1,2,4]triazole-3-sulfonylmethyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(4-methyl-4H-[1,2,4]triazole-3-sulfonylmethyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(1-methyl-1H-imidazole-2-sulfonylmethyl)-thiazol-2-yl]-urea-   1-[5-(1H-Imidazole-2-sulfonylmethyl)-thiazol-2-yl]-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-2-sulfonylmethyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-2-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-3-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-3-sulfonylmethyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-4-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-4-sulfonylmethyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-4-yloxymethyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-3-yloxymethyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-2-yloxymethyl)-thiazol-2-yl]-urea-   [4-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethoxy)-phenyl]-acetic    acid-   [4-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethylsulfanyl)-phenyl]-acetic    acid-   [4-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethanesulfonyl)-phenyl]-acetic    acid-   3-[4-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethoxy)-phenyl]-propionic    acid-   3-[4-(2-(3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethylsulfanyl)-phenyl]-propionic    acid-   3-[4-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethanesulfonyl)-phenyl]-propionic    acid-   4-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethylsulfanyl)-benzoic    acid-   4-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethanesulfonyl)-benzoic    acid-   4-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethoxy)-benzoic    acid-   N-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethyl)-acetamide-   N-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethyl)-methanesulfonamide-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-2-ylaminomethyl)-thiazol-2-yl]-urea-   2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethanesulfonyl)-1H-imidazole-4-carboxylic    acid-   2-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethyl]-1H-imidazole-4-carboxylic    acid-   2-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}thiazol-5-yl)-ethyl]-oxazole-4-carboxylic    acid-   2-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethyl]-1-methyl-1H-imidazole-4-carboxylic    acid-   2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-carboxylic    acid-   2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-carboxylic    acid amide-   2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-carboxylic    acid methylamide-   [(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-carbonyl)-amino]-acetic    acid-   [Methanesulfonyl-(2-{3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-carbonyl)-amino]-acetic    acid-   N-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-carbonyl)-methanesulfonamide-   (2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-acetic    acid-   2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-acetamide-   2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-N-methyl-acetamide-   [2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-acetylamino]-acetic    acid-   N-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-acetyl]-methanesulfonamide-   N-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethyl]-methanesulfonamide-   N-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethyl]-acetamide-   1-(5-Guanidinomethyl-thiazol-2-yl)-3-[2-(2-methoxy    benzoyl)-4-methyl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-(5-ureidomethyl-thiazol-2-yl)-urea-   1-{5-[3-(2-Dimethylamino-ethyl)-ureidomethyl]-thiazol-2-yl}-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   (2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethyl)-carbamic    acid 2-dimethylamino-ethyl ester-   (2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethyl)-carbamic    acid methyl ester-   [2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethyl]-carbamic    acid methyl ester-   1-[5-(2-Guanidino-ethyl)-thiazol-2-yl]-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(2-ureido-ethyl)-thiazol-2-yl]-urea-   {3-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethyl]-ureido}-acetic    acid-   1-(5-{2-[3-(2-Dimethylamino-ethyl)-ureido]-ethyl}-thiazol-2-yl)-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   [2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethyl]-carbamic    acid 2-dimethylamino-ethyl ester-   1-{5-[2-(1H-Imidazol-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-{5-[2-(1H-Imidazole-2-sulfonyl)-ethyl]-thiazol-2-yl}-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-{5-[2-(1-methyl-1H-imidazol-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-{5-[2-(1-methyl-1H-imidazole-2-sulfonyl)-ethyl]-thiazol-2-yl}-urea-   2-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethylsulfanyl]-1H-imidazole-4-carboxylic    acid-   6-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethylsulfanyl)-nicotinic    acid-   6-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethanesulfonyl)-nicotinic    acid-   2-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethylsulfanyl]-1-methyl-1H-imidazole-4-carboxylic    acid-   {4-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethylsulfanyl]-phenyl}-acetic    acid-   {4-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethanesulfonyl]-phenyl}-acetic    acid-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-{5-[2-(pyridin-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-{5-[2-(pyridine-2-sulfonyl)-ethyl]-thiazol-2-yl}-urea-   6-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethylsulfanyl]-nicotinic    acid-   6-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethanesulfonyl]-nicotinic    acid-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-(5-[1,2,4]oxadiazol-5-ylmethyl-thiazol-2-yl)-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(2-[1,2,4]oxadiazol-5-yl-ethyl)-thiazol-2-yl]-urea-   4-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-butyric    acid-   1-[5-(1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(1-methyl-1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-urea-   2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-sulfonyl)-1H-imidazole-4-carboxylic    acid-   2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-sulfonyl)-1H-imidazole-4-carboxylic    acid-   2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-sulfonyl)-1H-imidazole-4-carboxylic    acid-   1-[5-(1H-Imidazole-2-sulfonyl)-thiazol-2-yl]-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-3-sulfonyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-4-sulfonyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-4-ylsulfanyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-3-ylsulfanyl)-thiazol-2-yl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   6-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylsulfanyl)-nicotinic    acid-   6-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-sulfonyl)-nicotinic    acid-   1-(5-Methanesulfonyl-thiazol-2-yl)-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   3-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-sulfonyl)-propionic    acid-   3-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylsulfanyl)-propionic    acid-   1-(5-Bromo-thiazol-2-yl)-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   35    (5-Chloro-2-{3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-acetic    acid-   (5-Bromo-2-{3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-acetic    acid-   1-(5-Chloro-thiazol-2-yl)-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-(5-Chloro-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-(5-piperidin-1-ylmethyl-thiazol-2-yl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-(5-morpholin-4-ylmethyl-thiazol-2-yl)-urea-   1-(5-Dimethylaminomethyl-thiazol-2-yl)-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-(5-piperazin-1-ylmethyl-thiazol-2-yl)-urea-   1-[5-(4-Methyl-piperazin-1-ylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-[5-(4-Acetyl-piperazin-1-ylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-[5-(4-Methanesulfonyl-piperazin-1-ylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   (4-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethyl}-piperazin-1-yl)-acetic    acid-   2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-1H-imidazole-4-carboxylic    acid-   1-[5-(1H-Imidazol-2-ylsulfanylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-[5-(1-Methyl-1H-imidazol-2-ylsulfanylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(4H-[1,2,4]triazol-3-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-thiazol-2-yl]-urea-   (5-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-tetrazol-1-yl)-acetic    acid-   1-{5-[1-(2-Dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-thiazol-2-yl}-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   (5-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-tetrazol-1-yl)-acetic    acid-   1-{5-[1-(2-Dimethylamino-ethyl)-1H-tetrazole-5-sulfonylmethyl]-thiazol-2-yl}-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(1-methyl-1H-tetrazole-5-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(4H-[1,2,4]triazole-3-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(4-methyl-4H-[1,2,4]triazole-3-sulfonylmethyl)-thiazol-2-yl]-urea-   1-[5-(1-Methyl-1H-imidazole-2-sulfonylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-[5-(1H-Imidazole-2-sulfonylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridine-2-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridin-2-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridin-3-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridine-3-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridin-4-ylsulfanylmethyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridine-4-sulfonylmethyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridin-4-yloxymethyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridin-3-yloxymethyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridin-2-yloxymethyl)-thiazol-2-yl]-urea-   (4-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethoxy}-phenyl)-acetic    acid-   (4-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-phenyl)-acetic    acid-   (4-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-phenyl)-acetic    acid-   3-(4-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethoxy}-phenyl)-propionic    acid-   3-(4-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-phenyl)-propionic    acid-   3-(4-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-phenyl)-propionic    acid-   4-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-benzoic    acid-   4-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-benzoic    acid-   4-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethoxy}-benzoic    acid-   N-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethyl}-acetamide-   N-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethyl}-methanesulfonamide-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridin-2-ylaminomethyl)-thiazol-2-yl]-urea-   2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-1H-imidazole-4-carboxylic    acid-   2-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-1H-imidazole-4-carboxylic    acid-   2-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-oxazole-4-carboxylic    acid-   1-Methyl-2-(2-{2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-1H-imidazole-4-carboxylic    acid-   2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-carboxylic    acid-   2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-carboxylic    acid amide-   2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-carboxylic    acid methylamide-   ({2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-acetic    acid-   (Methanesulfonyl-{2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-acetic    acid-   N-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-carbonyl}-methanesulfonamide-   {2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-acetic    acid-   2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-acetamide-   N-Methyl-2-{2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-acetamide-   (2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-acetylamino)-acetic    acid-   N-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-acetyl)-methanesulfonamide-   N-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-methanesulfonamide-   N-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-acetamide-   1-(5-Guanidinomethyl-thiazol-2-yl)-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-(5-ureidomethyl-thiazol-2-yl)-urea-   1-{5-[3-(2-Dimethylamino-ethyl)-ureidomethyl]-thiazol-2-yl}-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   {2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethyl}-carbamic    acid 2-dimethylamino-ethyl ester-   {2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethyl}-carbamic    acid methyl ester-   (2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-carbamic    acid methyl ester-   1-[5-(2-Guanidino-ethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(2-ureido-ethyl)-thiazol-2-yl]-urea-   [3-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-ureido]-acetic    acid-   1-(5-{2-[3-(2-Dimethylamino-ethyl)-ureido]-ethyl}-thiazol-2-yl)-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   (2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-carbamic    acid 2-dimethylamino-ethyl ester-   1-{5-[2-(1H-imidazol-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-{5-[2-(1H-Imidazole-2-sulfonyl)-ethyl]-thiazol-2-yl}-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-{5-[2-(1-Methyl-1H-imidazol-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-{5-[2-(1-Methyl-1H-imidazole-2-sulfonyl)-ethyl]-thiazol-2-yl}-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   2-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethylsulfanyl)-1H-imidazole-4-carboxylic    acid-   6-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethylsulfanyl}-nicotinic    acid-   6-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethanesulfonyl}-nicotinic    acid-   1-Methyl-2-(2-{2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethylsulfanyl)-1H-imidazole-4-carboxylic    acid-   [4-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethylsulfanyl)-phenyl]-acetic    acid-   [4-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethanesulfonyl)-phenyl]-acetic    acid-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-{5-[2-(pyridin-2-ylsulfanyl)-ethyl]-thiazol-2-yl}-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-{5-[2-(pyridine-2-sulfonyl)-ethyl]-thiazol-2-yl}-urea-   6-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethylsulfanyl)-nicotinic    acid-   6-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethanesulfonyl)-nicotinic    acid-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-(5-[1,2,4]oxadiazol-5-ylmethyl-thiazol-2-yl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(2-[1,2,4]oxadiazol-5-yl-ethyl)-thiazol-2-yl]-urea-   4-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-butyric    acid-   1-[5-(1H-Imidazol-2-ylsulfanyl)-thiazol-2-yl]-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-[5-(1-Methyl-1H-imidazol-2-ylsulfanyl)-thiazol-2-yl]-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-Methyl-2-{2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-1H-imidazole-4-carboxylic    acid-   1-Methyl-2-{2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-sulfonyl}-1H-imidazole-4-carboxylic    acid-   2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-sulfonyl}-1H-imidazole-4-carboxylic    acid-   1-[5-(1H-Imidazole-2-sulfonyl)-thiazol-2-yl]-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridine-2-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridine-3-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridine-4-sulfonyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridin-4-ylsulfanyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridin-3-ylsulfanyl)-thiazol-2-yl]-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(pyridin-2-ylsulfanyl)-thiazol-2-yl]-urea-   6-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-nicotinic    acid-   6-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-sulfonyl}-nicotinic    acid-   1-(5-Methanesulfonyl-thiazol-2-yl)-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   3-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-sulfonyl}-propionic    acid-   3-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylsulfanyl}-propionic    acid-   1-(5-Bromo-thiazol-2-yl)-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   {5-Chloro-2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   {5-Bromo-2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-4-yl}-acetic    acid-   N-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-4-yl}-acetyl)-methanesulfonamide-   1-(4-Dimethylaminomethyl-thiazol-2-yl)-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-(4-piperazin-1-ylmethyl-thiazol-2-yl)-urea-   1-[4-(4-Methanesulfonyl-piperazin-1-ylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-(4-morpholin-4-ylmethyl-thiazol-2-yl)-urea-   2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-4-carboxylic    acid methylamide-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[4-(morpholine-4-carbonyl)-thiazol-2-yl]-urea-   {2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-4-ylmethyl}-carbamic    acid methyl ester-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-(4-ureidomethyl-thiazol-2-yl)-urea-   {2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-4-ylmethyl}-carbamic    acid 2-dimethylamino-ethyl ester-   1-(4-Guanidinomethyl-thiazol-2-yl)-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   (3-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-4-ylmethyl}-ureido)-acetic    acid-   1-{4-[3-(2-Dimethylamino-ethyl)-ureidomethyl]-thiazol-2-yl}-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   N-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-methanesulfonamide-   N-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-acetyl)-methanesulfonamide-   1-(4-Dimethylaminomethyl-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-(4-piperazin-1-ylmethyl-thiazol-2-yl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[4-(4-methanesulfonyl-piperazin-1-ylmethyl)-thiazol-2-yl]-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-(4-morpholin-4-ylmethyl-thiazol-2-yl)-urea-   2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-4-carboxylic    acid methylamide-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[4-(morpholine-4-carbonyl)-thiazol-2-yl]-urea-   {2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-carbamic    acid methyl ester-   1-(2-Isobutoxy-4-methyl-phenyl)-3-(4-ureidomethyl-thiazol-2-yl)-urea-   {2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-carbamic    acid 2-dimethylamino-ethyl ester-   1-(4-Guanidinomethyl-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea-   (3-{2-[3-(2-isobutoxy-4-methyl-phenyl)-ureido]-thiazol-4-ylmethyl}-ureido)-acetic    acid-   1-{4-[3-(2-Dimethylamino-ethyl)-ureidomethyl]-thiazol-2-yl}-3-(2-isobutoxy-4-methyl-phenyl)-urea-   N-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-4-ylmethyl)-methanesulfonamide-   N-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-4-yl)-acetyl]-methanesulfonamide-   1-(4-Dimethylaminomethyl-thiazol-2-yl)-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-(4-piperazin-1-ylmethyl-thiazol-2-yl)-urea-   1-[4-(4-Methanesulfonyl-piperazin-1-ylmethyl)-thiazol-2-yl]-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-(4-morpholin-4-ylmethyl-thiazol-2-yl)-urea-   2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-4-carboxylic    acid methylamide-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[4-(morpholine-4-carbonyl)-thiazol-2-yl]-urea-   (2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-4-ylmethyl)-carbamic    acid methyl ester-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-(4-ureidomethyl-thiazol-2-yl)-urea-   (2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-4-ylmethyl)-carbamic    acid 2-dimethylamino-ethyl ester-   1-(4-Guanidinomethyl-thiazol-2-yl)-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   [3-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-4-ylmethyl)-ureido]-acetic    acid-   1-{4-[3-(2-Dimethylamino-ethyl)-ureidomethyl]-thiazol-2-yl}-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   2-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-1H-imidazole-4-carboxylic    acid-   2-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-oxazole-4-carboxylic    acid-   2-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-1-methyl-1H-imidazole-4-carboxylic    acid-   2-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-amino)-1H-imidazole-4-carboxylic    acid-   2-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-amino)-oxazole-4-carboxylic    acid-   2-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-amino)-1-methyl-1H-imidazole-4-carboxylic    acid-   6-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-nicotinic    acid-   2-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-pyrimidine-5-carboxylic    acid-   5-({2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-1-methyl-1H-pyrazole-3-carboxylic    acid-   2-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-5-methyl-1H-imidazole-4-carboxylic    acid-   2-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-5-trifluoromethyl-1H-imidazole-4-carboxylic    acid-   1-{5-[2-(1H-Benzoimidazol-2-yl)-ethyl]-thiazol-2-yl}-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[2-(1H-imidazo[4,5-#b!]pyridin-2-yl)-ethyl]-thiazol-2-yl}-urea-   2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-1H-imidazole-4-carboxylic    acid-   2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-    ylmethyl}-1H-imidazole-4-carboxylic acid-   2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-oxazole-4-carboxylic    acid-   1-[5-(1H-Benzoimidazol-2-ylmethyl)-thiazol-2-yl]-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(1H-imidazo[4,5-b!]pyridin-2-ylmethyl)-thiazol-2-yl]-urea-   1-(5-Benzooxazol-2-ylmethyl-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(5-oxazolo[4,5-b!]pyridin-2-ylmethyl-thiazol-2-yl)-urea-   2-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-5-trifluoromethyl-oxazole-4-carboxylic    acid-   2-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-5-methyl-oxazole-4-carboxylic    acid-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[2-(4H-[1,2,4]triazol-3-yl)-ethyl]-thiazol-2-yl}-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[2-(4-methyl-4H-[1,2,4]triazol-3-yl)-ethyl]-thiazol-2-yl}-urea-   [3-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-[1,2,4]triazol-4-yl]-acetic    acid-   [5-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-tetrazol-1-yl]-acetic    acid-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[2-(1-methyl-1H-tetrazol-5-yl)-ethyl]-thiazol-2-yl}-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-{5-[2-(1H-tetrazol-5-yl)-ethyl]-thiazol-2-yl}-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-(2-[1,3,4]thiadiazol-2-yl-ethyl)-thiazol-2-yl]-urea-   2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazole-5-carboxylic    acid [1,3,4]thiadiazol-2-ylamide-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[5-([1,3,4]thiadiazol-2-ylaminomethyl)-thiazol-2-yl]-urea-   [2-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-imidazol-1-yl]-acetic    acid-   2-[(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-carbonyl)-amino]-1H-imidazole-4-carboxylic    acid-   2-[(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-carbonyl)-amino]-oxazole-4-carboxylic    acid-   2-[(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-carbonyl)-amino]-1-methyl-1H-imidazole-4-carboxylic    acid-   2-[(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethyl)-amino]-1H-imidazole-4-carboxylic    acid-   2-[(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethyl)-amino]-oxazole-4-carboxylic    acid-   2-[(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethyl)-amino]-1-methyl-1H-imidazole-4-carboxylic    acid-   6-[(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-carbonyl)-amino]-nicotinic    acid-   2-[(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-carbonyl)-amino]-pyrimidine-5-carboxylic    acid-   5-[(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-carbonyl)-amino]-1-methyl-1H-pyrazole-3-carboxylic    acid-   2-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethyl]-5-methyl-1H-imidazole-4-carboxylic    acid-   2-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethyl]-5-trifluoromethyl-1H-imidazole-4-carboxylic    acid-   1-{5-[2-(1H-Benzoimidazol-2-yl)-ethyl]-thiazol-2-yl}-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-{5-[2-(1H-Imidazo[4,5-#b!]pyridin-2-yl)-ethyl]-thiazol-2-yl}-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethyl)-1H-imidazole-4-carboxylic    acid-   2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethyl)-1H-imidazole-4-carboxylic    acid-   2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-ylmethyl)-oxazole-4-carboxylic    acid-   1-[5-(1H-Benzoimidazol-2-ylmethyl)-thiazol-2-yl]-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[5-(1H-Imidazo[4,5-#b!]pyridin-2-ylmethyl)-thiazol-2-yl]-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-(5-Benzooxazol-2-ylmethyl-thiazol-2-yl)-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-(5-oxazolo[4,5-#b!]pyridin-2-ylmethyl-thiazol-2-yl)-urea-   2-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethyl]-5-trifluoromethyl-oxazole-4-carboxylic    acid-   2-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethyl]-5-methyl-oxazole-4-carboxylic    acid-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-{5-[2-(4H-[1,2,4]triazol-3-yl)-ethyl]-thiazol-2-yl}-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-{5-[2-(4-methyl-4H-[1,2,4]triazol-3-yl)-ethyl]-thiazol-2-yl}-urea-   {3-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethyl]-[1,2,4]triazol-4-yl}-acetic    acid-   {5-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethyl]-tetrazol-1-yl}-acetic    acid-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-{5-[2-(1-methyl-1H-tetrazol-5-yl)-ethyl]-thiazol-2-yl}-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-{5-[2-(1H-tetrazol-5-yl)-ethyl]-thiazol-2-yl}-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-(2-[1,3,4]thiadiazol-2-yl-ethyl)-thiazol-2-yl]-urea-   2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazole-5-carboxylic    acid [1,3,4]thiadiazol-2-ylamide-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[5-([1,3,4]thiadiazol-2-ylaminomethyl)-thiazol-2-yl]-urea-   {2-[2-(2-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-thiazol-5-yl)-ethyl]-imidazol-1-yl}-acetic    acid-   2-({2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-1H-imidazole-4-carboxylic    acid-   2-({2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-oxazole-4-carboxylic    acid-   2-({2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-1-methyl-1H-imidazole-4-carboxylic    acid-   2-({2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-amino)-1H-imidazole-4-carboxylic    acid-   2-({2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-amino)-oxazole-4-carboxylic    acid-   2-({2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-amino)-1-methyl-1H-imidazole-4-carboxylic    acid-   6-({2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-nicotinic    acid-   2-({2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-pyrimidine-5-carboxylic    acid-   5-({2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-1-methyl-1H-pyrazole-3-carboxylic    acid-   2-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-5-methyl-1H-imidazole-4-carboxylic    acid-   2-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-5-trifluoromethyl-1H-imidazole-4-carboxylic    acid-   1-{5-[2-(1H-Benzoimidazol-2-yl)-ethyl]-thiazol-2-yl}-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-{5-[2-(1H-Imidazo[4,5-#b!]pyridin-2-yl)-ethyl]-thiazol-2-yl}-3-(2-isobutoxy-4-methyl-phenyl)-urea-   2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-1H-imidazole-4-carboxylic    acid-   2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-1-methyl-1H-imidazole-4-carboxylic    acid-   2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-ylmethyl}-oxazole-4-carboxylic    acid-   1-[5-(1H-Benzoimidazol-2-ylmethyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-[5-(1H-Imidazo[4,5-#b!]pyridin-2-ylmethyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(5-Benzooxazol-2-ylmethyl-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-(5-oxazolo[4,5-#b!]pyridin-2-ylmethyl-thiazol-2-yl)-urea-   2-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-5-trifluoromethyl-oxazole-4-carboxylic    acid-   2-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-5-methyl-oxazole-4-carboxylic    acid-   1-(2-Isobutoxy-4-methyl-phenyl)-3-{5-[2-(4H-[1,2,4]triazol-3-yl)-ethyl]-thiazol-2-yl}-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-{5-[2-(4-methyl-4H-[1,2,4]triazol-3-yl)-ethyl]-thiazol-2-yl}-urea-   [3-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-[1,2,4]triazol-4-yl]-acetic    acid-   [5-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-tetrazol-1-yl]-acetic    acid-   1-(2-Isobutoxy-4-methyl-phenyl)-3-{5-[2-(1-methyl-1H-tetrazol-5-yl)-ethyl]-thiazol-2-yl}-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-{5-[2-(1H-tetrazol-5-yl)-ethyl]-thiazol-2-yl}-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-(2-[1,3,4]thiadiazol-2-yl-ethyl)-thiazol-2-yl]-urea-   2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazole-5-carboxylic    acid [1,3,4]thiadiazol-2-ylamide-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[5-([1,3,4]thiadiazol-2-ylaminomethyl)-thiazol-2-yl]-urea-   [2-(2-{2-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-imidazol-1-yl]-acetic    acid-   2-({2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-1H-imidazole-4-carboxylic    acid-   2-({2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-oxazole-4-carboxylic    acid-   1-Methyl-2-({2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-1H-imidazole-4-carboxylic    acid-   2-({2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethyl}-amino)-1H-imidazole-4-carboxylic    acid-   2-({2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethyl}-amino)-oxazole-4-carboxylic    acid-   1-Methyl-2-({2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethyl}-amino)-1H-imidazole-4-carboxylic    acid-   6-({2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-nicotinic    acid-   2-({2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-pyrimidine-5-carboxylic    acid-   1-Methyl-5-({2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-carbonyl}-amino)-1H-pyrazole-3-carboxylic    acid-   5-Methyl-2-(2-{2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-1H-imidazole-4-carboxylic    acid-   2-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-5-trifluoromethyl-1H-imidazole-4-carboxylic    acid-   1-{5-[2-(1H-Benzoimidazol-2-yl)-ethyl]-thiazol-2-yl}-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-{5-[2-(1H-Imidazo[4,5-#b!]pyridin-2-yl)-ethyl]-thiazol-2-yl}-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethyl}-1H-imidazole-4-carboxylic    acid-   1-Methyl-2-{2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethyl}-1H-imidazole-4-carboxylic    acid-   2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-ylmethyl}-oxazole-4-carboxylic    acid-   1-[5-(1H-Benzoimidazol-2-ylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-[5-(1H-Imidazo[4,5-b!]pyridin-2-ylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-(5-Benzooxazol-2-ylmethyl-thiazol-2-yl)-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-(5-oxazolo[4,5-b!]pyridin-2-ylmethyl-thiazol-2-yl)-urea-   2-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-5-trifluoromethyl-oxazole-4-carboxylic    acid-   5-Methyl-2-(2-{2-[3-(4-methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-oxazole-4-carboxylic    acid-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-{5-[2-(4H-[1,2,4]triazol-3-yl)-ethyl]-thiazol-2-yl}-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-{5-[2-(4-methyl-4H-[1,2,4]triazol-3-yl)-ethyl]-thiazol-2-yl}-urea-   [3-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-[1,2,4]triazol-4-yl]-acetic    acid-   [5-(2-{2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazol-5-yl}-ethyl)-tetrazol-1-yl]-acetic    acid-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-{5-[2-(1-methyl-1H-tetrazol-5-yl)-ethyl]-thiazol-2-yl}-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-{5-[2-(1H-tetrazol-5-yl)-ethyl]-thiazol-2-yl}-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-(2-[1,3,4]thiadiazol-2-yl-ethyl)-thiazol-2-yl]-urea-   2-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-thiazole-5-carboxylic    acid [1,3,4]thiadiazol-2-ylamide-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[5-([1,3,4]thiadiazol-2-ylaminomethyl)-thiazol-2-yl]-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-[1,2,4]thiadiazol-5-yl-urea-   {5-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-[1,2,4]thiadiazol-3-yl}-acetic    acid-   N-{5-[3-(2-Cyclopentanecarbonyl-phenyl)-ureido]-[1,2,4]thiadiazol-3-ylmethyl}-methanesulfonamide-   1-(2-Cyclopentanecarbonyl-phenyl)-3-(3-methoxy-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-(3-ethyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-(3-methyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-(3-isopropyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-phenyl)-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Isobutoxy-phenyl)-3-[1,2,4]thiadiazol-5-yl-urea-   {5-[3-(2-Isobutoxy-phenyl)-ureido]-[1,2,4]thiadiazol-3-yl}-acetic    acid-   N-{5-[3-(2-Isobutoxy-phenyl)-ureido]-[1,2,4]thiadiazol-3-ylmethyl}-methanesulfonamide-   1-(2-Isobutoxy-phenyl)-3-(3-methoxy-[1,2,4]thiadiazol-5-yl)-urea-   1-(3-Ethyl-[1,2,4]thiadiazol-5-yl)-3-(2-isobutoxy-phenyl)-urea-   1-(2-Isobutoxy-phenyl)-3-(3-methyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Isobutoxy-phenyl)-3-(3-isopropyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Isobutoxy-phenyl)-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   1-[2-(2-Methoxy-benzoyl)-phenyl]-3-[1,2,4]thiadiazol-5-yl-urea-   (5-{3-[2-(2-Methoxy-benzoyl)-phenyl]-ureido}-[1,2,4]thiadiazol-3-yl)-acetic    acid-   N-(5-{3-[2-(2-Methoxy-benzoyl)-phenyl]-ureido}-[1,2,4]thiadiazol-3-ylmethyl)-methanesulfonamide-   1-[2-(2-Methoxy-benzoyl)-phenyl]-3-(3-methoxy-[1,2,4]thiadiazol-5-yl)-urea-   1-(3-Ethyl-[1,2,4]thiadiazol-5-yl)-3-[2-(2-methoxy-benzoyl)-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-phenyl]-3-(3-methyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(3-Isopropyl-[1,2,4]thiadiazol-5-yl)-3-[2-(2-methoxy-benzoyl)-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-phenyl]-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Piperidin-1-yl-phenyl)-3-[1,2,4]thiadiazol-5-yl-urea-   {5-[3-(2-Piperidin-1-yl-phenyl)-ureido]-[1,2,4]thiadiazol-3-yl}-acetic    acid-   N-{5-[3-(2-Piperidin-1-yl-phenyl)-ureido]-[1,2,4]thiadiazol-3-ylmethyl}-methanesulfonamide-   1-(3-Methoxy-[1,2,4]thiadiazol-5-yl)-3-(2-piperidin-1-yl-phenyl)-urea-   1-(3-Ethyl-[1,2,4]thiadiazol-5-yl)-3-(2-piperidin-1-yl-phenyl)-urea-   1-(3-Methyl-[1,2,4]thiadiazol-5-yl)-3-(2-piperidin-1-yl-phenyl)-urea-   1-(3-Isopropyl-[1,2,4]thiadiazol-5-yl)-3-(2-piperidin-1-yl-phenyl)-urea-   1-(3-Phenyl-[1,2,4]thiadiazol-5-yl)-3-(2-piperidin-1-yl-phenyl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-[1,2,4]thiadiazol-5-yl-urea-   {5-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-[1,2,4]thiadiazol-3-yl}-acetic    acid-   N-{5-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-[1,2,4]thiadiazol-3-ylmethyl}-methanesulfonamide-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(3-methoxy-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(3-ethyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(3-methyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(3-isopropyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-[1,2,4]thiadiazol-5-yl-urea-   {5-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-[1,2,4]thiadiazol-3-yl}-acetic    acid-   N-{5-[3-(2-Isobutoxy-4-methyl-phenyl)-ureido]-[1,2,4]thiadiazol-3-ylmethyl}-methanesulfonamide-   1-(2-Isobutoxy-4-methyl-phenyl)-3-(3-methoxy-[1,2,4]thiadiazol-5-yl)-urea-   1-(3-Ethyl-[1,2,4]thiadiazol-5-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-(3-methyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-(3-isopropyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Isobutoxy-4-methyl-phenyl)-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-[1,2,4]thiadiazol-5-yl-urea-   (5-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-[1,2,4]thiadiazol-3-yl)-acetic    acid-   N-(5-{3-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-ureido}-[1,2,4]thiadiazol-3-ylmethyl)-methanesulfonamide-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-(3-methoxy-[1,2,4]thiadiazol-5-yl)-urea-   1-(3-Ethyl-[1,2,4]thiadiazol-5-yl)-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-(3-methyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(3-Isopropyl-[1,2,4]thiadiazol-5-yl)-3-[2-(2-methoxy-benzoyl)-4-methyl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-methyl-phenyl]-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-[1,2,4]thiadiazol-5-yl-urea-   {5-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-[1,2,4]thiadiazol-3-yl}-acetic    acid-   N-{5-[3-(4-Methyl-2-piperidin-1-yl-phenyl)-ureido]-[1,2,4]thiadiazol-3-ylmethyl}-methanesulfonamide-   1-(3-Methoxy-[1,2,4]thiadiazol-5-yl)-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-(3-Ethyl-[1,2,4]thiadiazol-5-yl)-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-(3-methyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(3-Isopropyl-[1,2,4]thiadiazol-5-yl)-3-(4-methyl-2-piperidin-1-yl-phenyl)-urea-   1-(4-Methyl-2-piperidin-1-yl-phenyl)-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-[1,2,4]thiadiazol-5-yl-urea-   {5-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-[1,2,4]thiadiazol-3-yl}-acetic    acid-   N-{5-[3-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-ureido]-[1,2,4]thiadiazol-3-ylmethyl}-methanesulfonamide-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-(3-methoxy-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-(3-ethyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-(3-methyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-(3-isopropyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-fluoro-phenyl)-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(4-Fluoro-2-isobutoxy-phenyl)-3-[1,2,4]thiadiazol-5-yl-urea-   {5-[3-(4-Fluoro-2-isobutoxy-phenyl)-ureido]-[1,2,4]thiadiazol-3-yl}-acetic    acid-   N-{5-[3-(4-Fluoro-2-isobutoxy-phenyl)-ureido]-[1,2,4]thiadiazol-3-ylmethyl}-methanesulfonamide-   1-(4-Fluoro-2-isobutoxy-phenyl)-3-(3-methoxy-[1,2,4]thiadiazol-5-yl)-urea-   1-(3-Ethyl-[1,2,4]thiadiazol-5-yl)-3-(4-fluoro-2-isobutoxy-phenyl)-urea-   1-(4-Fluoro-2-isobutoxy-phenyl)-3-(3-methyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(4-Fluoro-2-isobutoxy-phenyl)-3-(3-isopropyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(4-Fluoro-2-isobutoxy-phenyl)-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   1-[4-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-3-[1,2,4]thiadiazol-5-yl-urea-   (5-{3-[4-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-ureido}-[1,2,4]thiadiazol-3-yl)-acetic    acid-   N-(5-{3-[4-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-ureido}-[1,2,4]thiadiazol-3-ylmethyl)-methanesulfonamide-   1-[4-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-3-(3-methoxy-[1,2,4]thiadiazol-5-yl)-urea-   1-(3-Ethyl-[1,2,4]thiadiazol-5-yl)-3-[4-fluoro-2-(2-methoxy-benzoyl)-phenyl]-urea-   1-[4-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-3-(3-methyl-[1,2,4]thiadiazol-5-yl)-urea-   1-[4-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-3-(3-isopropyl-[1,2,4]thiadiazol-5-yl)-urea-   1-[4-Fluoro-2-(2-methoxy-benzoyl)-phenyl]-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(4-Fluoro-2-piperidin-1-yl-phenyl)-3-[1,2,4]thiadiazol-5-yl-urea-   {5-[3-(4-Fluoro-2-piperidin-1-yl-phenyl)-ureido]-[1,2,4]thiadiazol-3-yl}-acetic    acid-   N-{5-[3-(4-Fluoro-2-piperidin-1-yl-phenyl)-ureido]-[1,2,4]thiadiazol-3-ylmethyl}-methanesulfonamide-   1-(4-Fluoro-2-piperidin-1-yl-phenyl)-3-(3-methoxy-[1,2,4]thiadiazol-5-yl)-urea-   1-(3-Ethyl-[1,2,4]thiadiazol-5-yl)-3-(4-fluoro-2-piperidin-1-yl-phenyl)-urea-   1-(4-Fluoro-2-piperidin-1-yl-phenyl)-3-(3-methyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(4-Fluoro-2-piperidin-1-yl-phenyl)-3-(3-isopropyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(4-Fluoro-2-piperidin-1-yl-phenyl)-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-[1,2,4]thiadiazol-5-yl-urea-   {5-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-[1,2,4]thiadiazol-3-yl}-acetic    acid-   N-{5-[3-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-ureido]-[1,2,4]thiadiazol-3-ylmethyl}-methanesulfonamide-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-(3-methoxy-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-(3-ethyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-(3-methyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-(3-isopropyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Cyclopentanecarbonyl-4-morpholin-4-yl-phenyl)-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Isobutoxy-4-morpholin-4-yl-phenyl)-3-[1,2,4]thiadiazol-5-yl-urea-   {5-[3-(2-Isobutoxy-4-morpholin-4-yl-phenyl)-ureido]-[1,2,4]thiadiazol-3-yl}-acetic    acid-   N-{5-[3-(2-Isobutoxy-4-morpholin-4-yl-phenyl)-ureido]-[1,2,4]thiadiazol-3-ylmethyl}-methanesulfonamide-   1-(2-Isobutoxy-4-morpholin-4-yl-phenyl)-3-(3-methoxy-[1,2,4]thiadiazol-5-yl)-urea-   1-(3-Ethyl-[1,2,4]thiadiazol-5-yl)-3-(2-isobutoxy-4-morpholin-4-yl-phenyl)-urea-   1-(2-Isobutoxy-4-morpholin-4-yl-phenyl)-3-(3-methyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Isobutoxy-4-morpholin-4-yl-phenyl)-3-(3-isopropyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(2-Isobutoxy-4-morpholin-4-yl-phenyl)-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   1-[2-(2-Methoxy-benzoyl)-4-morpholin-4-yl-phenyl]-3-[1,2,4]thiadiazol-5-yl-urea-   (5-{3-[2-(2-Methoxy-benzoyl)-4-morpholin-4-yl-phenyl]-ureido}-[1,2,4]thiadiazol-3-yl)-acetic    acid-   N-(5-{3-[2-(2-Methoxy-benzoyl)-4-morpholin-4-yl-phenyl]-ureido}-[1,2,4]thiadiazol-3-ylmethyl)-methanesulfonamide-   1-[2-(2-Methoxy-benzoyl)-4-morpholin-4-yl-phenyl]-3-(3-methoxy-[1,2,4]thiadiazol-5-yl)-urea-   1-(3-Ethyl-[1,2,4]thiadiazol-5-yl)-3-[2-(2-methoxy-benzoyl)-4-morpholin-4-yl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-morpholin-4-yl-phenyl]-3-(3-methyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(3-Isopropyl-[1,2,4]thiadiazol-5-yl)-3-[2-(2-methoxy-benzoyl)-4-morpholin-4-yl-phenyl]-urea-   1-[2-(2-Methoxy-benzoyl)-4-morpholin-4-yl-phenyl]-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   1-(4-Morpholin-4-yl-2-piperidin-1-yl-phenyl)-3-[1,2,4]thiadiazol-5-yl-urea-   {5-[3-(4-Morpholin-4-yl-2-piperidin-1-yl-phenyl)-ureido]-[1,2,4]thiadiazol-3-yl}-acetic    acid-   N-{5-[3-(4-Morpholin-4-yl-2-piperidin-1-yl-phenyl)-ureido]-[1,2,4]thiadiazol-3-ylmethyl}-methanesulfonamide-   1-(3-Methoxy-[1,2,4]thiadiazol-5-yl)-3-(4-morpholin-4-yl-2-piperidin-1-yl-phenyl)-urea-   1-(3-Ethyl-[1,2,4]thiadiazol-5-yl)-3-(4-morpholin-4-yl-2-piperidin-1-yl-phenyl)-urea-   1-(3-Methyl-[1,2,4]thiadiazol-5-yl)-3-(4-morpholin-4-yl-2-piperidin-1-yl-phenyl)-urea-   1-(3-Isopropyl-[1,2,4]thiadiazol-5-yl)-3-(4-morpholin-4-yl-2-piperidin-1-yl-phenyl)-urea-   1-(4-Morpholin-4-yl-2-piperidin-1-yl-phenyl)-3-(3-phenyl-[1,2,4]thiadiazol-5-yl)-urea-   4-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-4-yl}-2-methyl-butyric    acid-   2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-4,5,6,7-tetrahydro-benzothiazole-7-carboxylic    acid    Biological Assay    Glucokinase Activity Assay (I)

Glucokinase activity is assayed spectrometrically coupled to glucose6-phosphate dehydrogenase to determine compound activation ofglucokinase. The final assay contains 50 mM Hepes, pH 7.1, 50 mM KCl, 5mM MgCl₂, 2 mM dithiothreitol, 0.6 mM NADP, 1 mM ATP, 0.195 μM G-6-Pdehydrogenase (from Roche, 127 671), 15 nM recombinant humanglucokinase. The glucokinase is human liver glucokinase N-terminallytruncated with an N-terminal His-tag ((His)₈-VEQILA . . . Q466) and isexpressed in E. coli as a soluble protein with enzymatic activitycomparable to liver extracted GK.

The purification of His-tagged human glucokinase (hGK) was performed asfollows: The cell pellet from 50 ml E. coli culture was resuspended in 5ml extraction buffer A (25 mM HEPES, pH 8.0, 1 mM MgCl₂, 150 mM NaCl, 2mM mercaptoethanol) with addition of 0.25 mg/ml lysozyme and 50 μg/mlsodium azide. After 5 minutes at room temperature 5 ml of extractionbuffer B (1:5 M NaCl, 100 mM CaCl₂, 100 mM MgCl₂, 0.02 mg/ml DNase 1,protease inhibitor tablet (Complete® 1697498): 1 tablet pr. 20 mlbuffer) was added. The extract was then centrifugated at 15.000 g for 30minutes. The resulting supernatant was loaded on a 1 ml Metal ChelateAffinity Chromatography (MCAC) Column charged with Ni²⁺. The column iswashed with 2 volumes buffer A containing 20 mM imidazole and the boundhis-tagged hGK is subsequently eluted using a 20 minute gradient of 20to 500 mM imididazol in buffer A. Fractions are examined usingSDS-gel-electrophoresis, and fractions containing hGK (MW: 52 KDa) arepooled. Finally a gelfiltration step is used for final polishing andbuffer exchange. hGK containing fractions are loaded onto a Superdex 75(16/60) gelfiltration column and eluted with Buffer B (25 mM HEPES, pH8.0, 1 mM MgCl₂, 150 mM NaCl, 1 mM Dithiothreitol). The purified hGK isexamined by SDS-gel electrophoresis and MALDI mass spectrometry andfinally 20% glycerol is added before freezing. The yield from 50 ml E.coli culture is generally approximately 2-3 mg hGK with a purity >90%.

The compound to be tested is added into the well in final 2.5% DMSOconcentration in an amount sufficient to give a desired concentration ofcompound, for instance 1, 5, 10, 25 or 50 μM. The reaction starts afterglucose is added to a final concentration of 2, 5, 10 or 15 mM. Theassay uses a 96-well UV plate and the final assay volume used is 200μl/well. The plate is incubated at 25° C. for 5 min and kinetics ismeasured at 340 nm in SpectraMax every 30 seconds for 5 minutes. Resultsfor each compound are expressed as the fold activation of theglucokinase activity compared to the activation of the glucokinaseenzyme in an assay without compound after having been subtracted from a“blank”, which is without glucokinase enzyme and without compound. Thecompounds in each of the Examples exhibits activation of glucokinase inthis assay. A compound, which at a concentration of at or below 30 μMgives 1.5-fold higher glucokinase activity than the result from theassay without compound, is deemed to be an activator of glucokinase.

The glucose sensitivity of the compounds are measured at a compoundconcentration of 10 μM and at glucose concentrations of 5 and 15 mM.

While the invention has been described and illustrated with reference tocertain preferred embodiments thereof, those skilled in the art willappreciate that various changes, modifications and substitutions can bemade therein without departing from the spirit and scope of the presentinvention. For example, effective dosages other than the preferreddosages as set forth herein may be applicable as a consequence ofvariations in the responsiveness of the mammal being treated forglucokinase-deficiency mediated disease(s). Likewise, the specificpharmacological responses observed may vary according to and dependingon the particular active compound selected or whether there are presentpharmaceutical carriers, as well as the type of formulation and mode ofadministration employed, and such expected variations or differences inthe results are contemplated in accordance with the objects andpractices of the present invention.

Glucokinase Activity Assay (II)

Determination of Glycogen Deposition in Isolated Rat Hepatocytes:

Hepatocytes are isolated from rats fed ad libitum by a two-stepperfusion technique. Cell viability, assessed by trypan blue exclusion,is consistently greater than 80%. Cells are plated onto collagen-coated96-well plates in basal medium (Medium 199 (5.5 mM glucose) supplementedwith 0.1 μM dexamethasone, 100 units/ml penicillin, 100 mg/mlstreptomycin, 2 mM L-glutamine and 1 nM insulin) with 4% FCS at a celldensity of 30,000 cells/well. The medium is replaced with basal medium 1hour after initial plating in order to remove dead cells. Medium ischanged after 24 hours to basal medium supplemented with 9.5 mM glucoseand 10 nM insulin to induce glycogen synthesis, and experiments areperformed the next day. The hepatocytes are washed twice with prewarmed(37° C.) buffer A (117.6 mM NaCl, 5.4 mM KCl, 0.82 mM Mg₂SO₄, 1.5 mMKH₂PO₄, 20 mM HEPES, 9 mM NaHCO₃, 0.1% w/v HSA, and 2.25 mM CaCl₂, pH7.4 at 37° C.) and incubated in 100 μl buffer A containing 15 mM glucoseand increasing concentrations of the test compound, such as for instance1, 5, 10, 25, 50 or 100 μM, for 180 minutes. Glycogen content ismeasured using standard procedures (Agius, L. et al, Biochem J. 266,91-102 (1990). A compound, which when used in this assay gives ansignificant increase in glycogen content compared to the result from theassay without compound, is deemed to have activity in this assay.

Glucokinase Activity Assay (III)

Stimulation of Insulin Secretion by Glucokinase Activators in Ins-1ECells

The glucose responsive β-cell line INS-1E is cultivated as described byAsfari M et al., Endocrinology, 130, 167-178 (1992). The cells are thenseeded into 96 well cell culture plates and grown to a density ofapproximately 5×10⁴ per well. Stimulation of glucose dependent insulinsecretion is tested by incubation for 2 hours in Krebs Ringer Hepesbuffer at glucose concentrations from 2.5 to 15 mM with or withoutaddition of glucokinase activating compounds in concentrations of forinstance 1, 5, 10, 25, 50 or 100 μM, and the supernatants collected formeasurements of insulin concentrations by ELISA (n=4). A compound, whichwhen used in this assay gives an significant increase in insulinsecretion in response to glucose compared to the result from the assaywithout compound, is deemed to have activity in this assay.

1. A compound of Formula (Ib)

wherein R²⁴ is selected from the group consisting of F, Cl, Br, and—CH₃; L¹ is selected from the group consisting of -D-alkylene-E- and—O—; D is —O—; E is a direct bond; G¹ is selected from the groupconsisting of methyl, ethyl, propyl, butyl, isopropyl, isobutyl,sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidyl,piperidyl, hexahydroazepinyl, thiolanyl, tetrahydrothiopyranyl, andthiepanyl; L² is —N—(R²⁰)—; R²⁰ is H; L³ is —C(O)—; R¹ is hydrogen; G²is

R⁴³ is —C₁₋₆-alkylene-C(O)OR⁵⁴; R⁵⁴ is selected from the groupconsisting of hydrogen, methyl, ethyl, propyl, butyl, isopropyl,isobutyl, sec-butyl, tert-butyl, 3-pentyl, 2-pentyl, and 3-methyl-butyl;or a pharmaceutically acceptable salt or solvate thereof.
 2. Thecompound, pharmaceutically acceptable salt or solvate thereof of claim50, wherein G¹ is isobutyl.
 3. The compound, pharmaceutically acceptablesalt or solvate thereof of claim 50, wherein R²⁴ is methyl.
 4. Thecompound, pharmaceutically acceptable salt or solvate thereof of claim51, wherein R²⁴ is methyl.
 5. The compound, pharmaceutically acceptablesalt or solvate thereof of claim 50, wherein R⁵⁴ is hydrogen.
 6. Thecompound, pharmaceutically acceptable salt or solvate thereof of claim51, wherein R⁵⁴ is hydrogen.
 7. The compound, pharmaceuticallyacceptable salt or solvate thereof of claim 52, wherein R⁵⁴ is hydrogen.8. The compound, pharmaceutically acceptable salt or solvate thereof ofclaim 53, wherein R⁵⁴ is hydrogen.
 9. The compound, pharmaceuticallyacceptable salt or solvate thereof of claim 50, wherein R⁴³ is—CH₂—C(O)OR⁵⁴.
 10. The compound of claim 50, wherein the compound isselected from the group consisting of:{2-[3-(4-Methyl-2-[2-methypropoxy]phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester;{2-[3-(4-methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-aceticacid;{2-[3-(2-Cyclopropylmethoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester;{2-[3-(2-Cyclopropylmethoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid;{2-[3-(2-Cyclopentyloxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester; and{2-[3-(2-Cyclopentyloxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid, or a pharmaceutically acceptable salt or solvate thereof.
 11. Thecompound{2-[3-(4-methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-aceticacid or a pharmaceutically acceptable salt or solvate thereof.
 12. Apharmaceutical composition comprising the compound of Formula (Ib)

wherein R²⁴ is selected from the group consisting of F, Cl, Br, and—CH₃; L¹ is selected from the group consisting of -D-alkylene-E- and—O—; D is —O—; E is a direct bond; G¹ is selected from the groupconsisting of methyl, ethyl, propyl, butyl, isopropyl, isobutyl,sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidyl,piperidyl, hexahydroazepinyl, thiolanyl, tetrahydrothiopyranyl, andthiepanyl; L² is —N—(R²⁰)—; R²⁰ is H; L³ is —C(O)—; R¹ is hydrogen; G²is

R⁴³ is —C₁₋₆-alkylene-C(O)OR⁵⁴; R⁵⁴ is selected from the groupconsisting of hydrogen, methyl, ethyl, propyl, butyl, isopropyl,isobutyl, sec-butyl, tert-butyl, 3-pentyl, 2-pentyl, and 3-methyl-butyl;and a pharmaceutically acceptable carrier, diluent, excipient, ormixture thereof.
 13. The pharmaceutical composition of claim 61, whereinG¹ is isobutyl.
 14. The pharmaceutical composition of claim 61, whereinR²⁴ is methyl.
 15. The pharmaceutical composition of claim 62, whereinR²⁴ is methyl.
 16. The pharmaceutical composition of claim 61, whereinR⁵⁴ is hydrogen.
 17. The pharmaceutical composition of claim 62, whereinR⁵⁴ is hydrogen.
 18. The pharmaceutical composition of claim 63, whereinR⁵⁴ is hydrogen.
 19. The pharmaceutical composition of claim 64, whereinR⁵⁴ is hydrogen.
 20. The pharmaceutical composition of claim 61, whereinR⁴³ is —CH₂—C(O)OR⁵⁴.
 21. The pharmaceutical composition of claim 61,wherein the compound is selected from the group consisting of{2-[3-(4-Methyl-2-[2-methypropoxy]phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester;{2-[3-(4-methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-aceticacid;{2-[3-(2-Cyclopropylmethoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester;{2-[3-(2-Cyclopropylmethoxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid;{2-[3-(2-Cyclopentyloxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid ethyl ester; and{2-[3-(2-Cyclopentyloxy-4-methyl-phenyl)-ureido]-thiazol-4-yl}-aceticacid, or a pharmaceutically acceptable salt or solvate thereof.
 22. Apharmaceutical composition comprising the compound{2-[3-(4-methyl-2-[2-methylpropoxy]phenyl)-ureido]-thiazol-4-yl}-aceticacid or a pharmaceutically acceptable salt or solvate thereof; and apharmaceutically acceptable carrier, diluent, excipient, or mixturethereof.